3 Protein structure and function 1 Flashcards
Define and describe proteins
They are macromolecules
- they are amino acid polymers
- from 1 of more polypeptide chain
- amino acids vary in there physiological properties
Proteins fold in 3D:
- Function depends on 3D structure - determined genetically
Describe the hierarchy of protein structure:
4 levels of protein structure
- Primary - the Amino acid sequence (S=S bonds)
- Secondary - local packing and regular arrangements
- Tertiary - the 3D packing of secondary structure elements
- Quaternary - The number and arrangement of multiple polypeptides
Describe the structure of amino acids
Peptide bonds form between the amino and carboxyl groups of the amino acid
- Side chains (R-groups) are free to make chemical interactions (helping to define final structure)
Describe protein sequences
Convention - protein sequences are written N-terminal to C-terminal (left to right)
Notation:
- Using 3 letters (Ser-Gly-Tyr-Ala-Leu)
- Or 1 letter (SGYAL)
Describe sulphur containing side chains
2 amino acids that contain sulphur groups have a
unique role in proteins:
- Methionine (Met or M) - proteins always start with MET (not in mature protein)
- Cysteine (Cys or C) - Cys can form complexed with various metal ions
- Cys can also form disulphide bonds (not in cytosol)
(S=S)
Describe the nature of the peptide bond (in the amino acid)
2 amino acids bond together when a water molecule is formed
- these are amide linkages between the a-carboxyl group of one amino acid and the a-amino group of another AA
The peptide is a resonance hybrid
- π electrons delocalise over the entire bond, not just the C=O bond
- this gives a partial double bond character for N-C
Because N-C bond behaves like a double bond:
- rotation around N-C bond is restricted
- Region around NH-CO is planar
Describe peptide conformation
A peptide bond can assume a trans or cis conformation (due to the partial double bond nature of N-C)
The trans form is favoured 1000:1
- this is due to steric clash (less stable when both R groups are so close - leads to clash)
Trans = opposite (cis = same side)
Describe the main-chain conformation that is seen in an amino acid
The bond between residues (the peptide bond, between N-H and its adjacent CO) is planar
- but bonds within each amino acid residue can rotate (the bond between -NH and C and -CO and C)
- the angles formed are defined as phi and psi respectively (termed torsion or dihedral angles)
The conformations adopted help determine a protein’s overall shape
- Certain phi/psi angles are strongly favoured - this is to do with clashes of the chemical group
(that make it energetically unfavourable to adopt certain angles) and conformations
This reflects the formation of secondary structure
Describe the secondary structure of proteins
These are regular arrangements of the polypeptide that maximise main-chain hydrogen bondings and minimise steric clashes
The two most common types are:
- alpha (a) helices
- beta (ß) sheets
Describe alpha (a) helices as a type of secondary structure of the protein
It is a rigid, right-handed spiral structure
- consisting of a tightly-packed, coiled polypeptide backbone core
- with the side chains of the component L-amino acids extending outward from the central axis to avoid interfering sterically with each other
Describe the role of hydrogen bonds in the formation of alpha-helices in the secondary structure of proteins
Hydrogen bonds
- An a-helix is stabilised by extensive hydrogen bonds between the peptide bond carboxyl O and amide H that are part of the polypeptide backbone
- Hydrogen bonds are individually weak, but they collectively serve to stabilise the helix
Describe beta (ß) sheets as a type of secondary structure of the protein
Beta-sheets are formed from:
- 2 or more ß-strands (5-10aa in length).
- Hydrogen bonds are formed between residues that can be far apart in the primary sequence
A beta-sheet is formed by 2 or more peptide chains
- ß-sheets alinged laterally and stabilised by hydrogen bonds between the carboxyl O and amide H of amino acids that are either:
> intrachain (too far in a single nucelotide)
> interchain (in a different polypeptide chain)
The adjacent ß-strands are arranged either parallel or antiparallel to each other
- On each ß-strand, the R groups of adjacent amino acids extend in opposite directions, above and below the plane of the ß-sheet
Describe structural motifs, and explain how they can arise from secondary structure elements
Secondary structure elements can combine into larger units - ‘motifs’
- sometimes referred to as ‘supersecondary structural elements, they are secondary structures linked in specific combination by loops
They can be formed by the tight combining of a-helices, ß-sheets, and coils
- These form primarily the core region of the molecule
- they are connected by loop regions at the surface of the proteins
- some motifs have specific roles (e.g. DNA binding), but most are found in a wide range of functionally unrelated proteins
E.g.
- helix-turn helix
- beta-turn (or hairpin)
Describe the tertiary structure of a protein
A polypeptide’s tertiary structure refers to its exact 3D structure and the packing of the secondary structures within it
Polypeptides greater than 200 aa usually contain multiple ‘domains’
- these often serve as independent functional units
Describe how many proteins can act as ‘modular’
and the relation of Domains to this
Proteins are often modular structures, made up of a combination of structural and functional folds/domains
- Domains act as ‘scaffolds’
- loops provide functional stability
Domains are the fundamental functional and 3D structural units of the polypeptides
- the core of a domain is built from a combination of supersecondary structural elements (motifs)
