E2 Introduction to proteins Flashcards
what is binding of proteins characterised by?
- affinity: how strong the interaction is
- specificity: does it have the right association between amino acids for its binding
what are proteins made of?
amino acids
name some molecules that are proteins
- enzymes: highly efficient and specific catalysts
- receptors: sense and transmit signals via cascades of signal transduction pathways
- antibodies: part of our immune defence
what does chirality allow for in amino acids?
- 2 non-superimposable mirror images
- distinguished by optical rotation of plane of polarised light
- dextrorotatory (D, right) or laevorotatory (L, left)
- L amino acids are predominant in proteins
- D amino acids are rare in nature but are seen in bacterial cell walls and some antibiotics
what is the only amino acid that does not have a chiral carbon?
- glycine
- its R group is a hydrogen
how are hydrophilic amino acids sub-classified?
- according to charge at neutral pH
- basic (positive, amino groups)
- acidic (negative, carboxyl groups)
- polar (uncharged at neutral pH, negative and positive charges balance)
what happens to zwitterions as pH changes?
- higher pH / alkaline: lose proton (COO-)
- lower pH / acidic: gain proton (NH3+)
are aromatic side chains of amino acids hydrophilic or hydrophobic?
hydrophobic
describe cis and trans peptide chains
- cis means the R groups are on alternating sides of the chains
- trans means all the R groups are on the same side of the chain
describe the primary structure of proteins
- the linear sequence of amino acids in a polypeptide
- also includes the location of where other covalent bonds are possible eg. cysteine residues have potential for disulphide bonds
what are super-secondary structures?
- specific combination of several secondary structure elements
- bridge between secondary and tertiary structures
what are secondary structures?
- the localised organisation of a parts of a polypeptide
- involves hydrogen bonding
what are motifs in proteins?
- simple arrangement of structures that occur in more than one protein
- help ascertain function eg. a binding site
name 3 major secondary structures
- alpha helices
- beta-pleated sheets
- connecting loops (coils)
describe alpha helices
- repetitive local hydrogen bonding between carboxyl and amino groups with distinct spacing
- cylindrical, rod-like structures with R groups all positioned on the outside of the helix facing outwards
- right had twisting, 3.6 amino acids per turn
- hydrogen bonding occurs between carbonyl group of first amino acid and amino group of fifth (then second and sixth etc.)
which amino acid is a ‘helix-breaker’ and what does this mean?
- proline
- has a distinct hydrogen bond pattern and can’t participate in an alpha helix
- proline is often found at the end of an alpha helix forcing a directional change in the polypeptide
- proline can be found in other types of helix eg. collagen
describe beta-pleated sheets
- repetitive hydrogen bonding between alternating residues on adjacent sections of beta strands
- R groups protrude above and below the plane of the sheet
what is the difference between parallel and anti-parallel beta-sheets?
- parallel: polypeptide sections running in the same direction
- anti-parallel: polypeptide sections running in opposite directions
describe connecting loops (coils)
- not repetitive
- contain fewer backbone hydrogens
- sections that connect the regular structures of helices and sheets
what is the tertiary structure of a protein?
- the overall 3D arrangement of the polypeptide
- includes details of binding of any prosthetic groups eg. haem
- creates geometric relationships between distinct and often distant segments
what is the tertiary structure of a protein stabilised by?
non-covalent bonds:
- hydrogen bonds
- hydrophobic interactions
- ionic interactions
covalent bonds:
- disulphide bridges (can be intramolecular or intermolecular)
what are domains in proteins?
- distinct regions with a specific structure that performs a specific function
- often function and fold independently
what are the 2 main classes of domains in proteins?
functional:
- mediate a particular activity of the protein
- eg. ability to bind to DNA of an enzymatic activity
structural:
- a region of around 40 or more amino acids that form a stable secondary and tertiary structure
- often the domain can fold into this structure independently of the rest of the protein
what is quaternary structure of a protein?
- the association of 2 or more polypeptides into a multi-subunit complex
- stabilised by hydrogen bonds and van Der Waals forces
- may include prosthetic groups
what is meant by homomeric and heteromeric quaternary structure in proteins?
homomeric: identical polypeptide chains
heteromeric: different polypeptide chains
how are 3D structure and stability maintained?
- by a combination of non-covalent and covalent interactions
covalent:
- disulphide bonds
non-covalent:
- electrostatic forces
- van der Waals forces
- hydrogen bonds
- hydrophobic forces
what is required to assist the process of polypeptide folding?
accessory proteins (chaperones)
where is a hydrophobic R group most likely to be in a protein?
- buried inside the protein
- away from the hydrophilic environment
what is a disulphide bond?
- a covalent bond that forms between 2 cysteine residues closely located with each other in the final protein conformation
- however, they may be separated by many amino acids in the primary sequence
what is the function of a disulfide bond?
- facilitates intra and intermolecular bonding
- stabilises the overall 3D structure
how are disulfide bonds formed and where are they normally found?
- under oxidising conditions in the ER
- mainly found in secreted proteins and proteins of the extracellular matrix
what sector do structural motifs / folds fall into and what significance do they have?
- they are super-secondary structures
- they often mediate a similar function in different proteins eg. binding a particular ion or molecule
what do domains represent in proteins?
larger recognisable regions of proteins
what features usually make up larger proteins?
- structural motifs and domains
- these also occur in other proteins but with small variations and different combinations
describe the structural class of globular proteins
- high water solubility
- compactly folded
- includes most enzymes and transporters eg. haemoglobin
describe the structural class of fibrous proteins (scleroproteins)
- elongated proteins
- low water solubility
- large amounts of regular secondary structure
- often form stiff multimeric fibres
give 3 examples of fibrous proteins and describe one in detail
- collagen, elastin, keratin
- collagen is a triple, left-handed helix structure with each polypeptide having a regular repeating amino acid sequence of ‘Gly-Pro-X’
- many of these triple helix molecules pack together to form fibres
describe the structural class of integral membrane proteins and state examples of what kinds of proteins are included
- associated with membranes
- usually have alpha helices containing hydrophobic amino acids that span the hydrophobic, lipid region of the membrane
- includes receptors, transporters, cell-cell and cell-matrix proteins
what knowledge facilitated the discovery of new painkillers such as ibuprofen?
aspirin covalently binds and inactivates cyclooxygenases which produce prostaglandins and contribute to the sensation of pain associated with tissue inflammation
what is the name of the enzyme that degrades a protein?
protease
what kinds of proteins are difficult to access for proteases?
proteins with well-structures domains
how are most proteins degraded?
- by the ubiquitin-proteasome pathway
- multiple copies of the small protein ubiquitin are coupled to a lysine residue in the protein to be degraded by specific ligases (this is called polyubiquitination)
- a large protein complex called the proteasome recognises the polyubiquitin chain
- it unwinds the secondary structure of the ubiquitinated protein and hydrolyses it into small peptides
which amino acid is NOT found in alpha helical secondary structures?
proline
