3.2 - Protein structure and function Flashcards
what does a proteins sequence always start with and what is it coded by?
Met, coded for by AUG
N-terminus (2)
- start of polypeptide chain
- amino group (NH2)
C-terminus (2)
- end of protein chain
- carboxyl group (COOH)
what does the 5’-3’ of the mRNA sequence correspond to
the N-terminal to C-terminal of the polypeptide q
what do all amino acids contain (apart from proline) (3)
- acidic carboxyl group
- basic amino group
- hydrogen
what are the 2 ionisable protons in amino acids? (2)
- carboxylic acid
- amino group
what does ionisation of amino acids depend on?
pH (usually have 0 charge at physiological pH)
structure of amino acids
chiral (L isomer)
what has a different chemical property in amino acids?
each ‘R’ group
which amino acids are hydrophobic?
non-polar
where are hydrophobic amino acids found?
inside of cytosolic globular proteins
which amino acids are hydrophillic?
polar (able to form H-bonds)
which amino acids can form electrostatic interactions and are basic (+ve charge) or acidic (-ve charge)?
polar amino acids with charged side groups
which amino acid can form disulfide bonds?
cysteine
describe peptide bond formation
carboxyl group of one amino acid bonds to amino group of another amino acid, with elimination of a molecule of water (condensation reaction)
what is the structure of a protein dictated by? (2)
- properties of amino acid side chains
- partly by properties of the peptide bond
where are hydrophilic/hydrophobic amino acid residues found? (2)
- hydrophilic - predominantly on surface of protein
- hydrophobic - predominantly found in interior of protein (cystolic)
primary structure
linear sequence of amino acids linked by peptide bonds
secondary structure (2)
- 3D structure formed by H-bonds between peptide NH and CO groups
- folding of polypeptide chain into a-helices or B-sheets
tertiary structure (2)
- adopt specific 3D conformation, able to fulfil specific biological function
- achieved by numerous weak interactions between amino acid side chains
quaternary structure
some functional proteins composed of more than one polypeptide (association through non-covalent interactions)
a-helix (2)
- tightly coiled, rodlike structure
- R groups projecting out from axis of helix
B-sheet (3)
- formed by adjacent B-strands which have fully extended polypeptide (linked by H-bonds)
- strands may be parallel, antiparallel or mixed
- may be flat or twisted conformation
disulfide bonds
oxidation reaction can generate a cystine unite with a disulfide bond (comes from thiol SH)
globular protein domains
distinct 3D structural motifs
what is a domain
part of polypeptide chain that is independently stable or could undergo movement as single entity
example of a globular protein domain
kinase domain
how is modular construction of proteins possible?
through different domain combinations
what % of eukaryotic proteins have multiple structural domains
75%
how many domains do small proteins usually have
1
what are the 2 types of protein? (2)
- fibrous
- globular
what are the 2 solubilities of proteins? (2)
- water soluble
- lipid soluble
what is the role of fibrous proteins in nature?
structural
superfamily of structural (fibrous) proteins
coiled-coil proteins
give an example of a coiled-coil protein
a-keratin
properties of coiled-coil proteins and why (2)
- strong/flexible
- because of intertwining design
structure of fibrous proteins (2)
- two right-handed a-helices intertwining to form left-handed super helix
- further coiling into protofilaments and fibrils makes hair shaft
how is the structure of fibrous proteins stabilised?
ionic and van der waals interactions
globular protein structure
complicated and very compact 3D structure
what do the interior/exterior of globular proteins consist of? (2)
- interior - mainly hydrophobic amino acids (little/no space)
- exterior - charged/polar amino acids
how does hydrophobic amino acid distribution differ between fibrous/globular proteins? (2)
- fibrous - hydrophobic amino acids on outside of protein
- globular - hydrophobic amino acids inside protein
what is the role of membrane proteins?
interact with lipid bilayer, have specific sequences and structures
what type of protein are membrane proteins?
usually ‘inside out’ globular proteins (hydrophobic amino acids facing aqueous solution)
what proteins are targeted by majority of drugs?
membrane proteins - particularly receptors and enzymes, but also membrane transport proteins
GPCRs
G-protein-coupled receptors
structure of GBCRs
seven transmembrane a-helical domains, form huge protein family
examples of crucial protein-protein interactions (3)
- antibody-antigen recognition
- signals binding to receptors
- enzyme/substrate reactions
molecule (typically small) that binds to protein
ligand
how does ligand bind to protein (2)
- same non-covalent interactions that dictate protein structure
- induced fit model
enzyme role
catalyse making/breakdown of covalent bonds (facilitates formation of transition state)
2 fates of misfolded proteins (2)
- degraded by cellular quality control machinery
- form aggregates
what are various neurodegenerative diseases associated with?
accumulation of tau and a-Syn aggregates (taupathies and synucleinopathies)
what could be responsible for different neurodegenerative diseases?
aggregates adopting different structures
