MBB 322 Flashcards
Cell Compartments GCPR Neuronal Signalling RTKS Extracellular Matrix Cell-Cell Interactions Apoptosis Cell Cycle Cancer Stem Cells
What are 4 functions of biomembranes?
Compartmentalisation, selective permeable barrier, scaffolding for biochemical activities, responds to external signals
What are some key features of lipid biomembranes?
- Ampiphilic
- Impermeable to most water-soluble molecules
- Held by non covalent bonds
- Contains lipids, proteins, glycoproteins
- Asymmetrical
Three major classes of membrane lipids?
- Phosphoglycerides
- Sphingolipids
- Sterols
Tell me about Phosphoglycerides
- Most abundant type of phospholipids
- Also called glycerophospholipids
- Contains hydrophilic head group, unsatured tail, and saturated tail
What’s the difference between saturated and unsaturated fatty acids?
Saturated: straight, stackable, no double bonds
Unsaturated: double bond creates kink in carbon chain, reducing stackability
What do head groups do for phosphoglycerides?
Phosphodiester linked head groups affect interactions with other molecules in bilayer
- Different charges interact with different proteins
- Have signalling affects and can be used as 2ndary messengers
What are Phosphoinositides?
A type of phosphoglyceride that is used in different pathways (e.g. PI3 pathway) through the cleavage of its head group
What are Sphingolipids
- Derivatives of sphingosine, a long chain amino alcohol
- Sphingomyelin (SM) has a phosphocholine head group
- Sphingomyelin (SM) plus phosphoglycerides are
ALL Phospholipids!
What are glycolipids?
Sphingolipids with a sugar/sugar chain as a head group
- Found in non-cytosolic side of membrane
- Sugar groups added in golgi lumen
- Protects cells from harsh conditions
- Controls voltage and [Ca2+] at membrane surface
- Involved in cell adhesion
What are sterols?
Four carbon ringed compounds found in hormones that are usually messenger molecules
What forces affect the phospholipid bilayer formation?
- Hydrophobic effect aggregates hydrophobic groups together in the bilayer
- Bilayer stabilised by acyl chain van der Waals interactions
- Ionic/ H bond btwn polar heads interact with water
How do phospholipid bilayers spontaneously close?
- When mixed with water, lipids can form different types of aggregates due to their amphipathic nature
- Forming liposome sphere = most energetically
Why is lipid asymmetry important regarding glycolipids?
- Proteins can bind the cytosolic face where they require the negatively charged PS for activity
- PI is phosphorylated in response to extracellular signals and helps recruit intracellular signaling proteins to cytosolic face of membrane
How do membrane lipids move?
- Membrane asymmetry is created by
flippases, which are enzymes that
catalyze the “flip-flop” of lipids.
How do you measure lipid lateral movement?
Fluorescence Recovery After Photobleaching
How does lipid composition affect fluidity of the membrane?
Transition temperature is sensitive to the length and degree of saturation of fatty acyl tails of membrane lipids
- Cells can regulate their lipid composition to maintain a constant
membrane fluidity
What are lipid rafts?
Clusters of cholesterol, sphingolipids, and proteins (2-20nm)
- Slightly thicker than regular phospholipid areas
- More resistant to to non-ionic detergents
- Enriched in GPI anchored proteins and proteins anchored with fatty acid chains.
- Cholesterol makes the lipid bilayer less deformable and less permeable to water-sol molecules
What are the 4 ways of restricting the lateral mobility of plasma
membrane proteins?
A. Self-assembly in large
aggregates
B. Tethered by interactions with
molecules outside the cell
C. Tethered by interactions with
molecules inside the cell
D. Interactions with proteins on
the surface of another cell
How does the cortical cytoskeleton restrict the diffusion of lipids and
membrane proteins?
Protein diffusion within the plasma
membrane is 10 to 50 times slower
than in liposomes.
What are the 3 different ways proteins interact w/ the membrane?
- Transmembrane proteins
- Lipid anchored Proteins
- Membrane associated proteins
What is an alpha helix?
- Common secondary structure in membranes
- carbonyl oxygen atom of each peptide bond is hydrogenbonded
to the amide hydrogen of the amino acid four residues further along
the chain - formed by H bonds between the core or backbone atoms of amino
acids - Composed mainly of hydrophobic amino acids
What is a hydropathy plot?
Can predict potential a-helical
spanning membrane domains
- A positive value indicates that free energy is required for transfer of the segment to water
What are transmembrane proteins?
Transmembrane proteins can contain multiple a-helices
- Bacteriorhodopsin: a seven membranespanning a-helical protein
- Part of a large superfamily of membrane proteins with similar structure but different functions e.g.
G-protein coupled receptors
What are B-barrels
Another type of membrane spanning domain
- Abundant in outer membrane of gram-negative bacteria and the outer membrane of mitochondria and chloroplasts
- Many form pores in the membrane allowing the passage of small hydrophilic molecules
How does single pass transmembrane protein integrate with signal sequence into ER?
Lack a cleavable N-terminal ER signal
sequence.
* Instead have a (single) internal hydrophobic
signal-anchor sequence.
* Functions as both an ER signal sequence and
a membrane anchor sequence.
* The orientation of the protein into the
membrane is determined by the position of
positively charged amino acids flanking the
internal start transfer sequence.
how do proteins attach to the cytosolic leaflet?
Proteins can be attached to the cytosolic side of the membrane via a covalently attached fatty acid chain (acylation) or a prenyl group (prenylation)
* Farnesyl is a 15 carbon phenyl group. Intermediate in the cholesterol biosynthetic
pathway.
* Geranylgeranyl is a 20 carbon prenyl anchor.
how do proteins attach to the non-cytosolic leaflet?
Proteins can be attached to the noncytosolic side of the membrane by an oligosaccaharide
linker to the phospholipid phosphatidylinositol.
- This is called a glycosylphosphatidylinositol (GPI) anchor.
What are detergents?
At low concentration of detergent, molecules are monomers in solution. At the critical micelle concentration, they aggregate to form micelles
The concentration at which micelles are formed and the number of detergent molecules in a micelle is
specific for every detergent
Can purify functionally active membrane proteins
What’s the difference between integral and peripheral proteins?
Peripheral and integral membrane
proteins are distinguished by the conditions required to release them from the membrane
Peripheral
- changes in pH
* changes in ionic strength of buffer
* chelation of Ca2+
* addition of urea or carbonate
Integral proteins will be released by detergent solubilization
What is N-linked glycosylation?
- The 14 sugar residues are transferred from the special lipid molecule dolichol to the Asn side chain of a protein.
- The oligosaccharides then undergo
further processing in the lumen of the ER and Golgi. - Di-sulfide bond formation between Cys residues also occurs in the lumen of the ER.
What is O-linked glycosylation?
- Occurs on Ser and Thr residues in the lumen of the ER or the Golgi
- Variable number of sugars; from a few to hundreds
- Mucins, glycoproteins in mucus secretions are heavily O-linked glycosylated
- Proteoglycans, components of the
extracellular matrix, also heavily glycosylated
What is the purpose of glycosylation?
- Promotes protein folding and mediates binding of protein to chaperones
- Makes glycoproteins more resistant to proteolytic digestion
- Coats cells and protects them from pathogens, i.e. mucus coat of the lung and intestinal cells
- Recognised by proteins called lectins in the extracellular space which is important for cell adhesion
- Regulatory roles, i.e. the type of glycosylation can change specificity of receptors
- Modify a protein’s antigenic properties
e.g. Carbohydrates expressed on certain proteins and lipids on red blood cells and other cells
What is the general pathway for extracellular signalling to cellular response?
- Synthesis of signalling molecules
- Exocytosis if signalling molecules
- Binding of ligand to protein receptor
- Binding of ligand to receptor changes conformational chnange
- Receptor initiaties intracellular pathway
- Results in cellular function, metabolism, gene exp, shape, movement change
- Deactivation of receptor + removal of ligand
What can a signalling molecule (ligand) be?
Proteins, peptides, amino acids, nucleotides, steroids, retinoids, fatty acids, gases
What are the 5 different types of signalling?
- Paracrine
- Synaptic
- Endocrine
- Autocrine
- Contact-dependent
What are some examples of what acetylcholine can do to different types of cells?
- Acetylcholine in heart pacemaker cells can decrease rate of firing
- Acetylcholine in salivary gland cells cause secretion
- Acetylcholine in skeletal muscle cells can induce muscle contraction
What are the 2 classes of molecular switches and how do they work?
Kinases
- Phosphorylate through serine, threonine, and tyrosine groups
- Phosphorylation changes a protein’s charge and leads to conformation change
- Conform change alters ligand binding to increase/decrease activity of a protein
- phosphatases dephosphorylate
- 600 protein kinases and 100 protein phosphotases
GTPases
- Enzymes that hydrolyse GTP to GDP with 2 conformations
What do these stand for?
GAP
RGS
GDI
GEF
GAP: GTPase activating enzymes
RGS: Regulators of G protein signalling
GDI: Guanine nucleotide dissociation inhibitors
GEF: Guanine nucleotide exchange factors
What’s the difference between first and secondary messengers?
First messengers = ligand
Secondary messengers = small molcules that increase/decrease concentration in response to first messenger
What do these terms stand for?
PH
PTB
SH2
SH3
PH: PLeckstrin homology domain
PTB: Phosphoytrosine binding domain
SH2: Src homology 2 domain
SH3: Src homology 3 domain
How can signals and responses vary in different signalling pathways
- Response timing
- Sensitivity
- Dynamic Range
- Persistence
- Signal processing
- Integration
- Coordination
How can cells respond to increased signal?
All or none: Complete 100% activation on first messenger –> Positive feedback
Hyperbolic: Linear-like increase in activation depending on ligand
Sigmoidal: Exponential increase in activation until limit
What’s the difference between positive and negative feedback loops?
Positive feedbacks generate all or none responses
Negative feedbackloops create oscillatory responses that is based on system sensitivity
What are different ways cells adjust their sensitivity to a signalling molecule
- Receptor sequestration
- Receptor down-regulation
- Receptor inactivation
- Inactivation of signalling protein
- Production of inhibitory protein
How do GPCRs activate heterotrimeric G proteins
Ligand binding to GPCR –> conformation change in its 3 domains
Alterations of the alpha subunit of G protein allows exchange of GDP for GTP
Binding of GTP actiavtes a subunit to separate from by domain and acts as a GEF
Active Ga has affinity for an effector and activates it (e.g. adenylyl cyclase)
Hydrolysis of GTP to GDP in Ga dissociates form effector and reallocates with Gby
What does the activation of adenylyl cyclase do?
Adenylyl cyclase converts ATP to cAMP by removing 2 phosphates as pyrophosphate
The reaction is driven forward through GTP hydrolysis
Soon after cAMP is made, it is hydrolysed to 5`AMP by cyclic AMP phosphodiesterase to stabilise it
How is adenylyl cyclase controlled?
Epinephrine, gluacgon, ACTH = acitavtion of Gas protein to activate adenylyl cyclase
PGE1 and adenosine activate Gai protein to inhibit adenylyl cyclase
What are some examples of what cAMP increase concentration can do?
Adrenaline in muscle makes cAMP for glycogen breakdown
Adrenaline in heart makes cAMP to increase heart rate
Adrenaline in fat makes cAMP for triglyceride breakdown
What are agonists and antagonists?
Agonists: Mimic function of natural hormones and bind to its receptor to mimic normal responses
Antagonists: Occupy ligand binding sites on receptors blocking natural hormones and inhibiting receptor signalling
What is protein kinase A?
-A Serine/Threonine kinase activated by cAMP
- 2 regulatory subunits and 2 catalytic subunits
-4 cAMP molecules bind to the regulatory subunits to free up the catalytic subunits –> turns them active
- Binding of first cAMP molecule lowers the Kd for binding of second cAMP
- Causes signal cascading eventually making glucose
- Also can activate CREB which induces gene transcription through cAMP response elements
What happens if trimeric G proteins can’t be regulated?
Cholera toxin enzyme that catalyses transfer of ADP ribose from NAD+ onto a Gas subunit results in Gas subunit no longer hydrolysing bound GTP
–> Always active effector protein
How do you terminate response of GCPR signalling that activates adenylyl cyclase?
- Change in affinity of receptor for hormones when Ga is in GTP bound form
- Ga-GTP quickly hydrolysed –> decreases Ac activity
- cAMP phosphodiesterase hydrolyses cAMP to 5`-AMP
How do GCPRs activate phospholipase C?
- Ligand acivates trimeric protein
- Trimeric protein conformation change affinity to GTP
- Gaq dissociates with Gby and activates Phospholipase C
- PLC-B cleaves PIP2 to IP3 and DAG
Where does PIP2 come from in the PLC-B Pathway?
Phosphatidylinositol on fatty acid chains of the membrane is cleaved 2 times by PI kinase to form PI(4,5)P2
What do IP3 and DAG do in PLC-B pathway?
DAG acts as an activator for protein kinase C (not the main one but makes it more effective)
IP3 opens IP3 gated Ca2+ release channels in the lumen of endoplasmic reticulum and Ca2+ activates PKC
What processes can the release of Ca2+ do?
- Secretion of digestive enzymes in pancrease
- Secrection of amylase in salivary glands
- Muscle contractions in muscle
- Conversion of glycogen to glucose in liver
- Aggreagation of platelets
Tell me everything you know about calmodulin
-Ca2+ binds to four sites on calmodulin
- Regulates activity of many enzymes such as transcription factors, protein kinases, phophotases
- 4 Ca2+ binded = conformational change of calmodulni that wraps around target protein
How does CaM-Kinase II get activated from calmodulin?
- CaM-Kinase II has 6 active sites that can pop out of hexameric conformation
- Ca2+ and calmodulin release the active sites of CaM
- Allows for autophosphorylation of 2 phorylating domains
- Ca2+ independent state without calmodulin = 50%-80% active
- Protein phosphatase puts conformation back into regular state
What are some ways a cell terminates a Ca2+ response and maintains a low cytosolic concentration of Ca2+
- Na+ driven Ca2+ symporter out of cell
- Ca2+ pump out of cell
- Ca2+ pump into ER membrane
- Ca2+ binding molecules in cytoplasm
- Active Ca2+ import into mitochondrion
What are ion channels
- Allow movement of ions across membranes
- Can be voltage gated, ligand gated, or mechnanically gated from specific stimuli
Wtf is an electochemical gradient?
If a solute is charged both its concentration gradient and its electrical potential difference across the membrane influence its transport. These two factors can be combined to calculate the net driving force called electrochemical gradient.
- Almost all membrane in mammals have membrane potential of -70mV on cytosolic side
- Depends on potassiu eq and channels
- K+ gradient drives flow of ions hrough the reseting K+ channels genreated by Na+/K+ ATPases
How do G proteins regulate ion channels?
Many neurotransmitter receptors are G proteins that effect Na+ or K+ channels
How does the olfaction GPCR signalling pathway work?
Odorant compound activates Ga
Effector protein = AC3 –> Makes cAMP
cAMP activates growth hormone, kinases –> Transcripton factors –> gene transcription, activates Ca2+ coming into cytosol
How does visual transduction by rod photoreceptors work?
- Opsin covalently linked to chromophore11 in rhodposin, when hit by late, leads to conform change in heterotrimeric G protein transducin
- Activates PDE (GMP phosphodiesterase) effector protein that converts cGMP to GMP
- In dark, cGMP gated chanels are open and influx of + ions cause depolarisation of membrane –> in dark rod cell constantly secreteing neurotransmitter
How does nitric oxide affect as a signalling molecule?
Acetylcholine activates IP3 and Ca2+
- Influx of Ca2+ activates NO synthase to convert arginine into nitric oxide
- Nitric oxide diffuses across membranes and binds to guanylyl cyclase to activate it
- Guanylyl cyclase converts GTP to cGMP
- Rapid relaxation of smooth muscle cell
What are the 3 main types of neurons?
Sensory: Carry info to CNS
Motor: Carry info from CNS
Interneurons: Largest group located in CNS that connects sensory to motor
What is action potential?
Rapid, transient, all or none electrical activity propagated in plasma membrane of excitable cells
When an action potential reaches the nerve terminal in a presynaptic cell, it stimulates the terminal to release neurotransmitters that bind to ion channels to the post synaptic cells
How is action potential generated and propagated?
Opening of voltage gated Na+ channels result in depolisation of the membrane
Membrane depolarisation causes membrane refractory and resets Na+ channel
K+ channels open repolarise the membrane by restoring membrane potential + inactivation of Na+ channels
wtf is a myelin sheath and nodes of ranvier
Many vertebrate neurons are insulated by a myelin sheath –> increases speed at which axon can propagate action potential
- Schwann cells in PNS
- Oligodendrocytes in CNS
Insulation of axonal membrane so that little current can leak
Myelinated axon 1m/sec –> 100 m/sec
Na+ and K+ aren’t in insulated sections –> found in nodes of ranvier
Action potential jumps from node to node: Saltatory conductio
Tell me about synpases
- Neuronal signals transmitted from cell to cell at synapses
- Neurotransmitters are released by the presynaptic cell by exocytosis at synpatic cleft
- Bind to either ligand gated ion channels or GCPRS on post synaptic cell
- Neurotransmitters are derived from amino acids
- Excitatory: Open cation channels + cuase influx of Na+ and Ca+ to depolarise the post synaptic membrane
- Inhibitory: Opens K+ and Cl- channels for repolarisation
WTF IS A RECEPTOR TYROSINE KINASE
- Kinase with tyrosines that contain an extracellular ligand binding domain, single transmembrane domain, and a cytoplasm domain with kinase activity
- Identified as growth factors for different cells with many ligands/receptors commonly found when studying human cancers
What is dimerisation in RTKS?
RTKs have 2 kinase domains that can cross-phosphorylate each other by increasing activity of kinase domains that can phosphorylate other sites on the receptor
Activated through ligand binding to RTKs on exterior
How does the FGFR dimerisation mechanism work?
- Two FGF ligands tightly bind to heparan sulfate
- This association enhances ligand binding and formation of dimeric receptor complex
- Participation of heparan sulfate is essentil for efficient receptor activation
How does the EGF receptor dimerisation mechanism work?
- EGF receptors form an asymmetric kinase domain dimer
- One kinase domain pushes against the other kinase domain, thereby activating an activating conformation change
How do signal proteins bind to RTKs?
- Phosphorylated Tyr residue serves as a binding site for SH2 domain containing proteins and PTB domain containing proteins
- Protein domains might get activated or get phosphorylated on Tyr residues
- Phosphorylated/activated proteins release signalling proteins
How does RTK signalling in HER1 receptors mediate endocytosis and lysosomal degradation
- HER1 receptors have an avg healf life on cells of 1-15 hours
- After binding to EGF, endocytosis increased by 10x and most receptors degraded in lysosomes
- HER1 mutants lacking kinase activity don’t undergo accelerated endocytosis
-Covalent mods of receptors by mono-ubiquitinylation promotes endocytosis and degradation - Endocytosis also promotes signalling (e.g. nerve growth factors bind to receptors at axon termini) so. receptor complexes can undergo endocytosis can be trafficked to the cell body and provide a survival signal for the neuron
why ras ):
- Almost all RTKs activate the Ras/MAP kinase pathway
- Ras = small GTPase containing one or more covalently attached lipid groups that anchor protein to cytoplasmic face of PM
How do RTKs link to Ras?
- Binding of hormone (e.g. FGF) causes dimerisation + kinase activation of tyrosine residues
- GRB2 with SH2 domain attaches to ppho tyrosines and SH3 of GRB2 attaches to Sos
- Sos promotes dissociation of GDP from Ras and recruits GTP (dissociating from Sos)
What are the effects of Ras downstream of RTKs?
- PDGF and FGF ligands induce cell proliferation in fibroblast cells
- Microinjections of antibodies against Ras can inhibit proliferation
- Mutated Ras can also inhibit proliferation
- Always active Ras from mutations of glycine 12 to other AA can block the functional binding of Gap proteins (keping it always bound to GTP)
- Hyperactive Ras = 30% of human tumours
How can u measure close proximity of molecules?
FRET shines light at a protein and the light waves bounced off protein can predict if its interacting with another protein i think
Can use to measure if Ras is bound to GTP or GDP
How does Ras activate MAPK pathway?
Activated Ras actvates Raf (MAPKKK) which activates Mek (MAPKK) which activates Erk (MAPK)
- Raf and Erk = serine/threonine kinases
- Mek = dual specificity kinase
- Experiments discovered Raf/Mek/Efk downstream bc they deactivated Ras and none of them worked but deactivated Raf can still yield Ras results
Wtf do scaffolding proteins do to MAPK pathways?
Cells have a lot of MAPKKK pathways that shouldn’t affect each other so scaffolding proteins make sure the pathways stay separate and prevent cross talk
How does MAPK regulate transcription?
EGF and PDGF growth factors increase gene expression
- c-fos gene = TS factor necessary for cell cycle
- c-fos contains a serum response element that recognises SRF activated by p90 of MAPK to induce gene TS
What is an Eph receptor?
- Large family of RTKs
- ephrinAs = GPI anchored ligand
- ephrinB = transmembrane proteins with cytosolic tail ligand
- ephrinA binds to EphA and ephrinB binds to EphB
- Functions of Eph receptors induce vascular development, tissue border formation, cell migration, and axon guidance
- Regulate the cytoskeleton
How does EphA result in growth cone collapse?
- Coupling RTK to the actin cytoskeleton occurs through activation of Rho family GTPases
- Growth cone developing part of neuron that gives rise to synpatic axons
- EphA4 actiavtion activates Rho Gef
- Rho Gef puts RhoA in GTP active state
- Causes myosin mediated actin fillment contraction to collapse growth cones
What is reverse signalling?
A mechanism where membrane bound ligands also function as receptors to trigger intracellular events
What is the ECM
- Complex network of polysaccharides and proteins secreted by cells
- Determines shape and mechanical properties of organs and tissues
- Can hold cells and tissues together
- Can be dynamic and influence elasticity, cell shape and movements
What are 2. main types of ECM?
Basal Lamina: Thin sheet of ECM material underlying most epithelial cells and other organised groups of cells separating from connective tissue
Connective tissue: Material made up of fivers forming framework and support structure for body tissues and organs. Cartilage and bone = speccial connective tissue
The majority of volume is made up of ECM rather than cells
In connective tissue ECM matrix material is secreted largely by cells in the fibroblast family
What are the three classes of molecules in the ECM
- Proteoglycans provide the matrix in which structural proteins are embedded (polysaccharide protein complexes)
- Structural proteins such as collagens and elastins –> gives EC strength + elasticity
- Adhesive glycoproteins such as fibronectins and laminins which attach cells to the matrix
what the fuck is a proteoglycan
A group of glycoproteins that contain a core protein with one or more glycoaminoglycan chains attached.
HUH? What’s a GAG?
An unbranched polysaccharide chain composed of repeating disccharides with two sugars
- One amino sugar, another uronic acid
What are the four main classes of GAGs
- Hyaluronan, heparin, chondroitin, keratan sulfate
- Highly charged and hydrophilic- Althought 10% of ECM weight is fibrous proteins, it fills up most of ECM
- Attract bot water and cations and form a porous hydrated gel in which collagen/elastin fibrils become embedded
- Large amount of water creates turgor pressor allowing the matrix to withstand compressive forces
Hyaluronan?? WTF IS IT???
- Simplest GAG and acts as a space filler during tissue morphogenesis
- Up to 25k disaccharide units
- No sulpahated sugars
- Not covalently linked to any core proteins
- Made by PM bound enzyme cmoplex
- Major component of ECM around migrating + proliferating embryonic cells
- Forms a viscous gel lubricating properties thus abundant in joints –> shock absorber
- Also adds backbone of complex proteoglycans in cartilage
GAG Linkages??? HOW DO IT DO?
- Core proteins synthesised in RER and assembled sugars in golgi
- Either O or N linked oligosaccharides
- Sulfation occurs in golgi
Differences between proteoglycans and other glycoproteins
- Proteoglycans have at least one sugar side chain of proteoglycans that are GAG
- Proteoglycans have long unbranched chains of GAGs and the sugars can comprise most of the weight of the molecule
why r the proteoglycans diverse??
- Core proteins can be secreted or cell surface proteins that are integral membrane proteins or anchored by a GPI anchor
- Have diveristy in number, composition and seq of GAG chains
AGGRECANN WHAT IS ITTTTT
- Backbone is long molecule of hyaluronan
- Multiple aggrecan proteins attached non-covalently
- Protein backbone modified by GAGs
- Gel like properties –> resistant to compression forces in joints
huh what r the collagens gonna dooo?
- Most abundant in mammals 25% of body
- Long stiff triple helical standard structure
- Has Gly-Pro-Hydroxyproline repeats
- Human genome encodes 42 a-chains (diferent types of collagen)
- 3 a-chains wind together to form a helical rods, which is a fibril and the structural form of collagen
- Unique properties of each type of collagen are mainly due to differences in length, 3D structure, covalent modifications
How do collagens formed?
- Synthesis of individual a chains pro peptides in the rough ER
- Pro-peptides associate to form trimers and selected pro and lys residues are hydroylated
- Mod facilitate trimer formations and binding of the chaperone Hsp47
- Secretion and processing in golgi body
- Pro-peptide are cleaved by extracellular proteases to remove N and C terminus
- Trimers are staggered by 67nm, assembled into fibrils and covalently cross linked
what what what athwat what tpy e 1c ollage??
- In tendons type 1 collagens form long strong fibres with tensile strength
- Tendons connect muscles to bones and must withstand huge forces
- Minor fibrillar collages (type 5 and 9) coassemble with type 1 collagen into fibres
- Helps regulate properties of fibres
- Type I collagen fibrils are also used in the construction of bone
- Bone = 70% mineral and 30% protein mostly collagen type I
- Contain large amounts of the mineral dahllite = a crystalline calcium and phosphate containing mineral
- Cells secrete collagen fibrils that are then mineralised by depositiokn of small dahlite crystal
What do type 9 and 12 collagens tho?
Important in organisation of collagen fibrils
