Week 9 (Proteins (IV) Flashcards
What are globular proteins?
polypeptide chains fold into a spherical or globular shape
What are fibrous proteins?
polypeptide chains arranged in long strands or sheets
What are membrane proteins?
polypeptide chains fold into a spherical or globular shape that interacts with the lipid bilayer
What are the properties of fibrous proteins?
- Insoluble in water
- Usually consist of a single type of secondary structure
- Tertiary structure relatively simple
- Provide structural support and shape for cells and tissues
Fibrous proteins: describe the structure of α keratin
- α-helix, cross-linked by disulphide bonds between cysteine residues
- produces tough, protective structures of varying hardness & flexibility
What is the structure of α-keratin?
-Two right-handed α-helices intertwine to form a left-handed coiled coil
●Very stable, can be as long as 100 nm (1000 Å)
●60 members of this family in humans
●Including intermediate filaments of cytoskeleton & muscle protein myosin
Explain the structure and function of α-keratin?
Characterised by central regions of amino acids containing imperfect heptad repeats
●The structure is stabilised by van der Waals and ionic interactions between helices
●Can also have extensive disulphide bonding between the helices
●Number of disulphide bonds affects properties
●Hair & wool – fewer disulphides – more flexible
●Horns, claws, hooves – more disulphides - harder
Fibrous proteins: silk fibroin
- β conformation
- Soft, flexible filaments
Explain the structure and function of silk fibroin
Produced by insects and spiders
●Predominantly β-sheets
●Rich in Ala and Gly (small side chain) – permits close packing and interlocking of β-sheets
●Stabilised by hydrogen bonds and van der Waals interactions
Fibrous proteins: collagen
- Collagen triple helix
- High tensile strength, without stretch
Explain the structure and function of collagen
Main fibrous component of skin, bone, tendon, cartilage & teeth
●Unique secondary structure:
- Left-handed helix
- 3 amino acids per turn
●3 polypeptides supertwisted together in a right-handed coiled coil
●Every third residue is Glycine
●Contains hydroxylated amino acids
●Glycine – proline – hydroxyproline sequence is common
What is the cause of scurvy?
Inadequate hydroxylation of collagen is cause of scurvy – disease resulting from lack of Vitamin C
What is hydroxylation?
The of growing polypeptide chain. Free amino acids are not substrates
What is the hydroxylation reaction?
Amino acid + O2 + a-oxoglutarate =Hydroxyamino acid + CO2 + succinate
Cofactors/requirements
Fe2+, + O2, + Ascorbic acid (vitamin C)
Scurvy caused because of a lack of vitamin C which prevents the hydroxylation of amino acids
Proline unique structure important for the folding of collagen
- Proline causes steric hindrance and there is no N—H for hydrogen bonding in the polypeptide
- Proline causes steric hindrance – forces chain to fold up in its unique shape
Glycine in collagen
●Every third residue is Glycine
●Only glycine (smallest side chain) can fit in the centre of the coiled coil Interface has glycine thus allowing the helices to pack together
How do Peripheral membrane proteins interact with the membrane?
- Amphipathic alpha helix. (Align sideways along the helix)
- Hydrophobic loop. (Hydrophobic loops dip into the membrane and the hydrophilic parts remain outside)
- Lipidation. (Lipid part of the protein inserted into the membrane)
- Electrostatics (interactions with the hydrophilic phospholipid head groups)
Lipid anchored membrane proteins
●Lipids are covalently attached to the protein.
●These insert into the membrane, anchoring the protein.
●e.g. palmitate and myristate.
●May also be linked to glycosylphosphatidyl-inositol (GPI- tethered and stay on the outer surface of the cell)
●Present only in outer leaflet
Membrane protein secondary structure
●Majority of transmembrane proteins are composed of membrane spanning alpha-helices
●Can also have beta-barrels
Interactions with the bilayer
Structure of bacteriorhodopsin:
●A peripheral membrane protein
●Held in the membrane by a set of alpha helices with hydrophobic side chains
●7 transmembrane helices, each of which spans the bilayer.
●Large regions of the protein within the hydrophobic core of the bilayer
●need to have hydrophobic amino acid side chains
●Structure of prostaglandin synthase
What is Hydropathy plot analysis?
- It is used to characterize or identify possible structure or domains of a protein
- Can predict the presence of transmembrane alpha helices using algorithms that detect hydrophobic amino acids.
- The plot has amino acid sequence of a protein on its x-axis, and degree of hydrophobicity and hydrophilicity on its y-axis
Hydrophobic : between 0 and 3
Hydrophilic: between 0 and -3
May be helpful predict no of transmembrane helices e.g. if a stretch of about 20 amino acids shows positive for hydrophobicity, these amino acids may be part of alpha-helix spanning across a lipid bilayer
What is Side chain localisation?
- Hydrophobic side chains protrude into the bilayer core
- Charged and polar side chains in the aqueous phases either side of the membrane
- Positive-inside rule
- Tyrosines and tryptophans often located at the water-lipid interface
Channels or transporters may have hydrophilic residues in the translocation pore
●Porin
●Outside residues hydrophobic
●Central water-filled pore lined with charged and polar residues
Membrane proteins are not soluble in water
●Need to use detergents to solubilise membrane proteins from a bilayer
●Detergents have hydrophobic and hydrophilic regions.
What are the functions of membrane proteins?
- intracellular joinings
- enzymatic activity
- transport (active and passive)
- cell-cell recognition
- anchorage/attachment
- signal transduction
