Secondary Proteins Flashcards
What is a polypeptide?
A polymer of amino acid residues linked by peptide bonds (amide linkages)
Describe the peptide bond?
Rigid, planar structure
With 40% double-bind character - due to resonance interactions
What information supports the properties of the peptide bond?
The peptides C-N bond is 0.13 A shorter than its N-C alpha single bond
The C=O bond is 0.02 A longer than normally in aldehydes and ketones
What conformation are most peptide bonds?
Trans (one up and one down in the bond)
The bond is in the amide plane
This is more energetically favourable to avoid steric interferences
Except 10% of Proline - they follow cis peptide bonds
What are torsion angles between peptide groups?
They describe polypeptide chain conformations
The backbone/main chain are the atoms participating in the peptide bonds (no side chains)
Therefore the conformation of the backbone can be described by torsion angles - also calle dihedral angles
What are the torsion angles?
Rotation around C alpha (in the middle) C-N and C-C
ϕ and Ψ angles
They are both defined as 180 degrees when the polypeptide chain is fully extended
The conformational freedom is therefore sterically restrained
What indicates allowed conformations of polypeptides?
Ramachandran Diagram - the sterically allowed ϕ and Ψ angles
What are notable exceptions to the generic areas of the Ramachandran diagram?
Proline is the most conformationally restricted amino acid
Glycine is the least sterically hindered - therefore can assume conformations forbidden to other residues
What are the regular secondary structures of proteins?
Alpha helix
Beta pleated sheet
They are regular as they are composed of sequences of residues with repeating ϕ and Ψ angles
Describe the alpha helix?
Right handed helix Ideal: ϕ=−57° and Ψ=−47° 3.6 residues per turn 5.4 A pitch Avg length 12 residues Avg turns 3.3 = 18 A
Amino acid side chains project outwards to avoid steric clashes
How is the backbone arranged within the alpha helix?
The peptide C=O bond of the nth residue points along the helix axis toward the peptide N—H group of the (n+4)th residue
= strong H bonds almost optimum distance of 2.8 A
What is a property of the alpha helix?
They are amphipathic due to ‘faces’ of side chains
The whole coil is a dipole
How is the alpha helix finished off?
The First 3 N-H and the last 3 C=O are not H bonded
But
They can twist to form an N-cap and a C-cap
= helix capping
Describe the beta-pleated sheet?
They are formed from 2 or more chains/sheets
The Hydrogen bonds occur between neighbouring polypeptide chains to form sheets (two types):
Antiparallel - neighbouring polypeptide chains running in opposite directions (most energetically favourable and stable, reaching full H bond potential)
Parallel - H bonded chains run in the same direction
Describe the measurements of beta pleated sheets?
Each strand of a β sheet has a two-residue repeat with a repeat distance of 7.0 Å
Up to 15 residues, avg of 6 residues
2-22 polypeptide strands, avg of 6 strands
Can be amphipathic
How do polypeptides strands within a beta pleated sheet connect?
They produce a right handed twist due to interactions between chiral L-amino acid residues
Antiparallel - small ordered turn
Parallel - crossover loop (with a lack of regular angles)
How can secondary structures be linked together?
Using reverse turns or beta bends - they mostly occur at protein surfaces
It involves the arrangment of 4 successive amino acids
What is a classification of proteins, based on repeating structures?
Fibrous - protective, connective and supportive roles
Globular - often used in catalysis/metabolism
What is keratin?
A coiled coil
Mechanically durable and relatively unreactive
Outer epidermal layer of skin, in hair, nails and horns
Two a-keratin polypeptides twist around each other to form a left handed coil
What is higher order keratin?
Multiple dimers form a protofilament
Protofilaments dimerise to form protofibril
4 protofibrils form microfibril
α Keratin is rich in Cys residues, which form disulfide bonds that cross-link adjacent polypeptide chains
It is deemed hard or soft depending on the quantity of high or low sulfur content
Describe collagen?
Extracellular protein
Strong tensile strength (due to hydrophobic interactions and cross-links)
Components of connective tissues e.g. bone, teeth, cartilage, tendon etc…
One collagen molecules = 3 polypeptide chains
Left handed polypetide helices twisted to form a right handed superhelical structure - it has interchain H bonding for stability
What is collagen made from?
Glycine (33%), proline (15-30%) and Y
Y - PTM either:
3-hydroxyprolyl
4-hydroxyprolyl
5-hydroxyprolyl
What disease can result in association to collagen?
Scurvy
Skin disease due to lack of vitamin C
Vitamin C is used to maintain the enzyme prolyl hydroxylase
This enzyme is used in the PTM of proline
What other collagen related diseases are there?
Osteogenesis imperfecta - brittle bone disease
A single aa change distorts the helix as only glycine can sterically fit every 3 residues = reduction in stability
4 types
Ehlers-Danlos syndrome - characterised by the hyperextensibility of joints and skin (super stretchy skin)
What is hydropathy?
How hydrophobic an amino acid is
We can predict a secondary structure and solvent exposure from the amino acid sequence i.e. if it is buried or on the outside
In what ways will an amino acid sequence affect the secondary structure potentially negatively?
A beta pleated sheet with an ‘extra’ residue not hydrogen bonded to a neighbouring strand = a beta bulge
Proline will produce a kink in a helix or b sheet
Steric clashes between large branched side chains e.g. Ile and Tyr = destablisiation of a helices
Describe globular proteins?
Compact and spheroidal
Contain alpha helices and/or beta sheets in different proportions
The primary sequence lacks repeating sequence motifs
Nearly all main and side chain groups in the interior that can H-Bond do so
Most enzymes are globular
e.g. haemoglobin
Describe fibrous proteins?
Highly elongated and structurally simple compared with globular proteins
Secondary structure = dominant structural motif
Made of simple repeating amino acid sequence, e.g. silk and collagen
Provide strength and/or flexibility to structures and are therefore found in materials with a protective, connective or supportive role, e.g. skin, tendons, hair
