Week 2 Flashcards
parts of an amino acid
- alpha carbon to which all other atoms and groups are attached
- amino group (NH2)
- carboxyl group (COOH)
- R group - side chain
how is a peptide bond formed?
- there is a reaction between the carboxyl group on one amino acid and the amino group on the other.
- the OH group on the carboxyl end of one amino acid reacts with the hydrogen atom on the amino group of the other to eliminate a molecule of water
what two features are always present in polypeptides, even in short chains?
an amino end (N-terminus) and a carboxyl end (C-terminus)
residues
what amino acids are referred to as once they have joined together into a polypeptide chain
in an alpha helix, where does hydrogen bonding occur between residues?
- there is hydrogen bonding between an oxygen atom of the carbonyl group of residue ‘n’ and the hydrogen atom of the amide group of the residue ‘n+4’ on the same polypeptide chain
- this is repeated in a regular fashion (1 and 5, 2 and 6, 3 and 7)
- the peptide chain thus twists around on itself and forms a cylindrical structure (a stable alpha helix)
are R-groups involved in the formation of alpha helices?
no
give the hierarchy of protein structure and examples for each
- primary; AA sequence
- secondary; local folding, like alpha helix and beta sheet
- tertiary; long-range folding, essentially 3D structure
- quaternary; multimeric organisation (the organization of multiple polypeptide chains with respect to each other)
- multiprotein complexes
major categories of amino acids
- acidic: negatively charged
- basic: positively charged
- uncharged polar: tends to form H=bonds, interact with h2o on the outside of proteins
- non polar: on the inside of proteins, ‘hydrophobic core’ due to hydrophobic interactions. found in lipid bilayer
what type of amino acids usually have enzymatic functions?
polar amino acids
what is unique about the structure of cysteine?
- contains interchain disulphide bonds
- whether these occur can be controlled by the cell based on redox conditions
- helps the protein hold its shape with physical or chemical stress
how is the primary structure of a protein numbered?
from the amino group (N-terminus)
give an example of how differences in primary amino acid sequence matter
- vasopressin and oxytocin
- both are 9AA long neuropeptide hormones
- AA sequence is identical except at 2 positions
- vasopressin controls urine production rates and oxytocin is involved in birth, lactation, and pair bonding
give an example of how the order of AA’s is important too
- Leu-Enkephalin (pentapeptide N-Tyr-Gly-Gly-Phe-Leu-C) is a natural opioid peptide which down modulates the perception of pain
- the pentapeptide N-Leu-Phe-Gly-Gly-Tyr-C, basically a reversal, has no pharmacological effects
- the NH2-COOH orientation of the peptide is essential for function
describe the structure of the beta sheet
- H-bonding between carbonyl oxygen (C=O) of 1aa and amide hydrogen (N-H) of aa in neighbouring strand
- R groups not involved but alternately project up and down
- beta sheets typically contains 4-5 beta strands but can have more than 10
types of beta sheets
- anti-parallel
- parallel
where are beta sheets found
strong, rigid structure found in silk
compare and contrast hydrogen bonding in alpha helices and beta sheets
- H bonds formed between carbonyl oxygen, amide hydrogen in peptide backbone
Alpha: - 4 AA’s apart and within the same segment of
pp chain
Beta: - Between AA’s in different segments or
strands of pp chain
coiled coil
- when alpha helices are twisting together
- amphipathic alpha helix
- these are found in alpha-keratin of skin, hair, and also myosin motor proteins
- helices wrap around each other to minimise exposure of hydrophobic amino acid side chains to aqueous environment
tertiary structure
- 3D overall structure of a protein
- held together by hydrophobic interactions, non-covalent bonds (hydrogen bonds, dipole-dipole and van der Waals), and covalent disulphide bonds
What determines the confirmations into which proteins fold?
proteins generally fold into the conformation that is the most energetically favourable
what helps fold proteins?
Proteins will fold into the shape dictated by their
amino acid sequence, but chaperone proteins help make the process more efficient and reliable
in living cells.
3 types of hydrogen bonding within tertiary structure of a protein
backbone to backbone: hydrogen bond between atoms of two peptide bonds
backbone to side chain: hydrogen bond between atoms of a peptide bond and an amino acid side chain
side chain to side chain: hydrogen bond between atoms of two amino acid side chains
What are protein domains?
- portion of a protein that has its own tertiary structure, often functioning in a semi-independent manner
- eukaryotic proteins often have 2 or more domains connected by intrinsically disordered sequences
- domains are important for the evolution of proteins
domains are often specialised for
different functions
Src protein kinase
- contains SH3 domain, SH2 domain, and kinase domain with 2 lobes
- phosphorylates amino acids to change the activity of proteins
- SH2 regulates kinase domain
- SH3 regulates kinase domain in a different way
- kinase domain phosphorylates the amino acids
protein families
- have similar amino acid sequences and tertiary structures
- however, members have often evolved to have different functions
- most proteins belong to families with similar structural domains
quaternary structure
proteins that have more than one polypeptide chain
describe haemoglobin
- 4 separate polypeptide chains
- 2 alpha subunits and 2 beta subunits
- each subunit is a separate polypeptide
- sickle cell anaemia is caused by a mutation in the beta subunit
give 3 types of multi protein complexes
- many identical subunits (eg actin filaments)
- mixtures of different proteins and DNA/RNA (eg viruses and ribosomes)
- very dynamic assemblies of proteins to form molecular machines (eg machines for DNA replication initiation or for transcription)
scaffold proteins
assemble other proteins needed for a particular process, getting them close together so work can be carried out
how are proteins studied?
- first purify protein/proteins of interest via various types of electrophoresis and affinity chromatography
- then determine amino acid sequence (eg mass spectrometry)
- discover precise 3D structure using techniques such as x ray crystallography, nuclear magnetic resonance spectroscopy or cry-electron microscopy
what properties can be exploited to separate proteins from one another so they can be studied individually?
- size, shape, charge, hydrophobicity, and their affinity for other molecules.
AI used to predict protein structure
alphafold to predict protein structure from linear amino acid sequences
proteomics
large scale study of proteins
- identity and structure of proteins
- protein-protein interactions, regulation of these interactions and their position within a pathway
- abundance and turnover of proteins
- location within a cell or tissue
- bioinformatics, statistics, and artificial intelligence often in combination with other ‘omics’ data
