protein structure and function.

What is a peptide vs a protein

• Dipeptides: two amino acids joined together 

• Tripeptides: three amino acids joined together

• Short polypeptides (10-40 amino acids long)

• Large polypeptides (proteins) (>40 aa )

• Large proteins - found mostly in the muscles

what are N and C terminals

• First amino acid has free NH3⁺ group → N-terminal end →   left side

• Last amino acid has free COO⁻ group → C-terminal →   end right side

describe the features of peptide bond

• peptide bond is bteween the COOh and NH2 of another amino acid they join and water is lost  

• has features of a partial double bond because of the partially negative o and partially positive N 

• shorter than expected C-N bond length

• Stronger than expected C-N bond

• There is no free rotation around a peptide bond

  • This is because it is a rigid C-N bond, no rotation

• Joined amino acids are usually in the trans arrangement of groups

•  R groups are opposite- trans r groups same side - cis 

how is a peptide bond formed and broken

• condensation reactions form peptide bond (very strong)

— Water is lost

— Formed by enzyme reaction 

• Hydrolysis breaks them apart  - adding water

what are the 4 levels of protein structure

• Primary – sequence of amino acids in the peptide chain.

• Secondary – folding  the peptide chain ( into an α-helix or β-sheet).

• Tertiary – the overall structure of one folded peptide chain

• Quaternary – more than one folded peptide chain joined together – (sub units put together) e.g. haemoglobin has 4 polypeptide chains

what are the forces that stabilise proteins structure

• Non–covalent

  • Hydrogen bonds

  • Electrostatic interactions (ionic bonds)

  • Van der Waals forces 

  • Hydrophobic effect

• Covalent bonds between the sidechains include:

  • Disulfide bridges (not all proteins have them, cysteine has these)

explain how hydrogen bonds form and its features

• Form when a hydrogen atom covalently bonded to a highly electronegative atom (O, N, or F) becomes partially positive (δ⁺).

• This hydrogen is then attracted to another electronegative atom (O, N, or F) with a partial negative charge (δ⁻)nearby.

• Strength depends on which atoms are involved.

• Hydrogen bonds are weaker than covalent bonds but may have partial covalent character.

what are electrostatic interactions

• They are ionic bonds (salt bridges) formed between oppositely charged side chains 

• — e.g. positively charged lysine/arginine and negatively charged aspartic/glutamic acid. At physiological pH, their side chains are ionised (NH₃⁺ and COO⁻), allowing attraction.

whata are van der waal forces and hwo are they formed

• it is an intermolecular force between side chains 

• VDWs are dependent on dipole effect caused by the unequal distribution of electrons

  • Random movement if electrons cause a temp dipole 

  • This induces a dipole on neighbouring molecules 

  • VDW are The attraction between the Partial negative δ- and partial δ+ 

  • Makes a  δ- and  δ+ charge across the covalent bond 

What is the role of hydrophobic interactions in protein folding/clumping?

• Hydrophobic (non-polar) side chains can’t form H-bonds with water.

• Water becomes more ordered → decreasing entropy (unfavourable).

• To avoid this, proteins fold so hydrophobic residues are buried inside and hydrophilic (polar) residues face out.

• This is the main driving force for soluble protein folding.

• Causes clumping of non-polar regions.

what is a disulfide bridge

• A covalent bond that contributes to protein structure

• Disulfide (S-S) bridges between two Cys residues (residues = side chain/R group)

• Joining subunits together e.g. insulin

what are the 3 protein secondary structures

• α-helix

•  β-sheet

•  loops and turns.

formed by hydrogen bonds between atoms in petptide bond

describe alpha helix bond

• Hydrogen bonds form between the O in C=O and H in N–H every 4th peptide bond (within the same chain)

• The helix spins right-handed

• 3.6 residues per turn - the left over amino acid when water is removed  

• pitch length:  0.54nm length from each complete turn 

• forms a rigid, cylinder-like structure giving structural support.

• R groups project outward (hydrophobic in membrane proteins)

explain how beta sheets form

• Linear peptide chains align side by side.

• Can be parallel (same direction) or antiparallel (opposite directions).

• Hydrogen bonds form between the H of –NH and the O of –CO groups on different chains.

• These H-bonds hold the strands together, forming a β-sheet structure.

describe and explain the 2 beta sheet structures

1.  Antiparallel- the strands are in opposite directions, one from N -> C the other from C->N terminals- these are more stable as the hydrogen bonds are straight 

2.  Parallel - all strands  run from the N to C terminals - these Hydrogen bonds are slanted so less stable 

what are loops and turns

• Loops and turns are joining sections for beta sheets, turns are shorter than loops

• A type of secondary structure 

do all proteins have the same combination of alpha and beta subunits

no

what is a super secondary structure

• a recurring pattern of α-helices and β-sheets in proteins.

• not a tertiary structure

• Examples: α/β-barrel, β-barrel, Rossmann fold

explain the tertiary stucture

• How the whole polypeptide (subunit) is folded in 3D 

• it has many different secondary and/or super secondary structures (domains).    

• Formed by the interaction of them amino acids side chains ( the R group)

what is a Domains of proteins

• A domain is a part of a protein that can fold independently into a stable 3D shape.

• Each domain often has a specific function, e.g. binding a molecule, catalysing a reaction, or interacting with other proteins.

• One protein can have one or several domains, giving it multiple functions.

explain the quaternary structure

• How the whole functional protein is formed in 3D,

• it may consists of a number of subunits 

• the amino acids side chains from 2 different units interact with non covalent bonds

describe the structure of collagen

• Triple helix structure 

• three polypeptide chains ( called alpha chains)

• Hydrogen bonds between the chains 

• 3 residues in each turn

• Left handed helix ( spins left direction)

- Glycine, proline, hydroxy-proline are the repeating sequence of amino acids in the collagen chain 

- GLY-X-Y-GLY-X-Y

              X= mainly proline 

              Y= mainly hydroxyproline 

How do membrane proteins arrange their side chains in a lipid environment?

• Membrane proteins sit in a non-polar lipid environment.

• Hydrophobic (non-polar) side chains face  into the membrane.

• Polar side chains face the aqueous environments at the top and bottom.

• This arrangement allows signal transmission between the cell’s inside and outside.

How can mutations affect protein folding and cause disease?

• Mutations can cause proteins to fold incorrectly.

• Misfolded proteins may build up into stable clumps.

• Examples:

  • B-RAF mutation → tumours like Langerhans cell histiocytosis granuloma.

  • Amyloid proteins → plaques in Alzheimer’s disease.

  • Prion proteins → convert to pathogenic forms in Creutzfeldt–Jakob disease.