Proteins - Block 3 Flashcards
What is the structure of a collagen molecule like?
It is a triple-stranded helical filament, with three helical α chains wrapping around each other.
How does glycine influence the structure of collagen?
Gly residues exist in the core of the helical strand, facilitating the tight packing of the three strands.
How can collagen be cross-linked to form fibrils and then fibres?
Lysine residues form intramolecular and intermolecular cross-links (Lys-Lys crosslinking). The resulting fibrils aggregate in the same way to form a fibre.
What is the role of elastin?
Elastin endows tissues with elasticity.
Elastic fibres in the ECM provide resilience to recoil.
How does elastin’s structure result in its mechanism of elasticity?
> It contains α-helical segments with Lys residues, as well as long hydrophobic regions,
> The K residues can cross-link to form a 2D network, facilitated by lysyl oxidase,
> When a force, the unstructured hydrophobic segments can extend, and they can recoil back to the original position thanks to the cross-linked α-helical segments.
What is the role of fibronectin?
> It anchors cells and helps with cell migration <
a. It cross-links ECM molecule & links cells to the matrix, and b. it forms fibres
What is the basal lamina?
> > A specialised ECM «
> Underlying epithelia
> Surrounds muscle cells
> Acts as a filter in the kidney
What is the role of laminin?
> Important component of basal lamina
> Facilitates formation of 2D networks
> Interacts with other ECM proteins like type IV collagen “molecular sea” and perlecan
What are 4 functions of sophisticated local cell-cell //EGM partnerships? (L.O.)
- Imparting mechanical properties
- Enabling cells to recognise & co-operate each other
- Allow for the dynamic nature of tissues
- Allow selective diffusion of molecules
What two broad categories of subunit assemblies can a protein have?
- Identical//similar subunits
> Defined small number (haemoglobin)
> Defined large number (a few viruses)
> Variable number (MTs, actin, clathrin coats) - Several distinct subunits
(nuclear pores, molecular machines)
Meaning & examples of a (1) full-time complex?
> Function as stable oligomer
Several subunits
Icosahedral or helical symmetry
e.g. haemoglobin, polio virus
Meaning & examples of a (2) part-time complex?
> Function as oligomer AND individual subunits
e.g. G-proteins, rhodopsin
Meaning & examples of a (3) transient complex?
> Occur briefly in signal cascade
Rapid transmission of information
e.g. Ras and Raf (GTP binding to one complex causes affinity for the other to decrease & the complex breaks down).
Meaning & examples of a (4) dynamic assembly?
> Rapid assembly//disassembly
AT//GTP-controlled
e.g. Actin (dynamic filaments) & tubulin (road network)
Which motor protein carries cargo to the + end of the microtubule?
Kinesin
Which motor protein carries cargo to the - end of the microtubule?
Dynesin
What functions does an Actin filament have?
> Mechanical support
Cytoplasm traffic routes
Cell migration
Muscle contraction
What functions does a MT have?
> Trafficking cargo
> Separating chromosomes
What are three examples of molecular machines?
> Proteosome
GroEL//GroES
Nuclear Pore
What is (MM1) the Proteosome?
> “Garbage-disposal machine”
Recognises + unfolds old proteins (caps)
Proteolytic sites cut chain up (inner chamber)
What is (MM2) GroEL//GroES?
> A folding machine.
Chamber lets in polypeptide; ATP binds, causing GroES cap to bind & its polar inner surface helps prevent competing reactions, allowing protein to fold.
When protein is made, ATP is hydrolysed and GroES cap opens up.
What is (MM3) the Nuclear Pore?
> Pore in the nucleus
Very complex structure
Made of 456 protein molecules
What are the 4 components of communication & their roles? (L.O.)
- Signal molecules = Messengers
- Receptors = Signal Transducers
- Intracellular Sig. Pathways = 2nd messengers
- Target effector = Transcription regulator
What are the 4 types in intercellular communication? (L.O.)
A. Contact-dependent
B. Paracrine (cell > cell signal molecules)
C. Synaptic
D. Endocrine (bloodstream)
What FORM is the information in cell signalling?
Signal molecules
How is the signal READ in cell signalling?
Receptor proteins
How is the read signal COMMUNICATED in cell signalling?
Intracellular signal pathway (2nd messenger)
What EFFECT does the communicated signal have in cell signalling?
Influences the effector protein (which controls transcription)
What are the 3 classes of cell SURFACE receptors?
- Ligand-gated channels
- G-protein coupled receptors (GPCRs)
- Enzyme-linked receptors
What is the basic architecture of a GPCR?
GOOD TO KNOW
> 7 hydrophobic helical domains
> Extracellular loops N-terminal loops (ligands bind here!)
> Intracellular C-terminal loops (trimeric G-proteins associate here)
What is the basic structure of a GPCR-associating G-Protein?
GOOD TO KNOW
> α, β and γ regions
> α is a GTPase.
α can dissociate from β and γ subunits, which then form a heterodimer.
Where is the GTP//GDP binding site on a GPCR-associating G-Protein?
α has the GTP//GDP binding site at its interface with the β//γ subunits.
How is a GPCR-associating G-Protein anchored to the inside of the membrane?
With a fatty acyl PT-modification that’s usually on the β//γ subunits.
What regions of a GPCR-associating G-Protein are conformationally sensitive (cause a shape change)?
The “Switch Regions” on the α subunit that bind the outer PO4 of GTP.
What is the effect of the α region of a G-protein dissociating?
> It binds to a GTP
The active conformation is activated
This interacts with effector proteins
What does the β//γ heterodimer do when the α region of a G-protein dissociates?
It modulates other effector proteins.
What causes the dissociated α region of a G-protein to re-associate?
> RGS proteins accelerate its hydrolysis of ATP
> It becomes inactive again
What happens when dissociated α is inactivated (to complete the cycle)?
> It re-associates with β//γ
GDP is released
The G-protein re-associates with the GPCR
What two factors influence the function of GPCRs?
GOOD TO KNOW
- Ligand binding to the GPCR
2. Influence of RGS proteins on the α active site
What is the general action of a GPCR?
GOOD TO KNOW
- α subunit binds to membrane effector
- Effector activated; generates 2nd messengers
- GTP hydrolysed to GDP & dissociates
- α can now re-associate with β//γ
What does the effects caused by different signals depend upon?
which signalling-pathway proteins are being expressed inside the cell.
What are the characteristics of epithelial tissue?
GOOD TO KNOW
> Cells are tightly bound into sheets.
Not much ECM; thin layer (lamina).
cell-cell adhesions attach the cells & bear mechanical stress.
What are the characteristics of connective tissue?
GOOD TO KNOW
> Cells are distributed sparsely.
Plentiful ECM.
Rich in fibrous polymers; matrix bears the mechanical stress.
What are the three broad types of cell junction?
GOOD TO KNOW
- Tight Junctions - Zip cells together, regulate molecular transport between cells.
- Anchoring Junctions - Attach cells to each other and the ECM.
- GAP Junctions - Mediate chemical//electrical signals.
What does the ECM provide for cells?
A habitat in which they can build & maintain solid structures.
List some important components of the ECM.
IMPORTANT
> Glycosaminoglycans (GAGs): massive hydrated polysaccharides that form a gel OR attach to core proteins to make proteoglycans.
> Collagens: Principal ECM component, fibrous protein.
> Elastin: Forms a network that stretches when mechanical force is applied and relaxes again.
> Fibronectin: Links cells to ECM and each other (cross-linking). Has protein binding sites, some of which are cryptic and can only be revealed when the fibronectin fibrils are stretched. Interacts with actin; cells can migrate through the ECM along fibronectin fibrils.
> Laminin: Forms 2D network in basal lamina. Also a ligand for integrin and has binding sites.
In what way is the ECM dynamic?
There is significant two-way information exchange between ECM and cytoskeleton via integrins.
