Protein And Protein Structure Flashcards
What are some functions of proteins?
-enzymes
-storage
-structural
-transport
-defence (antibodies)
-regulatory
-receptors
-contractile
How many proteins are roughly in humans
100,000
what shapes can proteins appear in?
-globular
-fibrous (elongated)
-membrane spanning (need to be hydrophobic)
what are the different protein structures?
-primary - sequence of amino acids
-secondary - local regions formed into regular structures
-tertiary - folding of polypeptide into 3D conformation
-quaternary - multiple subunits
describe amino acids
-chiral molecules
-only 20 naturally occurring aa
-only L forms of the aa are used by cells (left-handed)
-consist of tetrahedral alpha carbon w amine and carboxyl groups and organic side chain
what is the ionisation state at different pHs?
-low pH -amide group is +ve
-high pH - carboxyl group is -ve
-neutral pH - both groups are charged
what are some drivers of the shape of proteins?
-amino acid sequence
-chaperones
-water (will cause hydrophilic R group amino acids to be on outside)
-disulfide bonds
-H bonds
-flexibility
what kind of buffer are aa?
weak buffer
What is the isoelectric point?
-the pH at which the molecule is electrically neutral
-avg of pK values on both side of neutral
describe peptide bonds
-rigid
-planar
-stable and covalent
-physiologically broken by proteases
-avg protein has 300 peptide bonds
what is post-translational modification?
-enzyme mediated modification of proteins after synthesis
-this changes properties of proteins
what are examples of post-translational modifications?
-glycosylation - addition of carb
-cleavage
-lipid addition
-oxidation, carboxylation, acetylation
-phosphorylation
what does phosphorylation of proteins do?
- changes shape
-changes charge
-activates protein
-switches kinases on
-switched phosphatases off
what does side chain (R group) affect?
-size
-charge
-shape
-reactivity
-H bonding
-Determines protein shape & function
how can aa be classified chemically?
-polar/non-polar
-acidic/basic
how can aa be classified structurally?
-aliphatic/aromatic
-sulphur containing
-charged
how can aa be classified structurally?
-aliphatic/aromatic
-sulphur containing
-charged
describe dentin phosphoryns
-made up of aspartic acid (35-45%) and serine (40-55%)
-highly negatively charge and acidic
-regulate bio-mineralisation
-binds to collagen I and Ca2+
how does aa structure relate to function?
Overall conformation gives protein its function
Binding specificity, flexibility, solubility, degradability
Position of amino acid side chains in 3D space
what are the different protein structures?
-primary - linear sequence of amino acids
-secondary - local regions formed into regular structures
-tertiary - folding of polypeptide into 3D conformation
-quaternary - multiple subunits
describe Secondary protein structure
Polypeptide chains can fold into regular structures
α helix
β pleated sheet
Structural motifs e.g. turns
Non regular coils & loops- more flexible e.g. hinges
Describe the alpha helix
-tightly coiled rod
-globular, DNA binding, membrane spanning proteins
-H bonds bw NH and CO groups
-some amino acids form alpha helices more than other e.g. met, ala, glu, lys
-major structural motif for haemoglobin
-two or more alpha helices can entwine to form a cable e.g. keratin
describe b pleated sheets
-H bonds form bw two parts of the protein that can be far apart
-H bonds are optimal when pleated
-can occur in same or opposite direction
describe Haemoglobin
α helices: major structural motif
Two or more α helices can entwine to form a cable eg keratin
describe b turns
-non regular
-4 amino acids
-hairpin loop
-H bonds formed
-v stable
describe structural motifs
Grouping of a few secondary structural elements e.g. helix-turn-helix
Can occur in several proteins and carries out same function
how are zinc finger proteins an example of structural motifs?
α helix, antiparallel β pleated sheet, Zinc coordinated by two His & two Cys residues
Mediates DNA/RNA binding
describe the tertiary structure of proteins
-folding pattern of secondary structure
-3D structure provides binding sites for ligands
-maintains appropriate residue on surface - polar for aqueous, hydrophobic for membranes
-physically independent regions called domains
describe chaperones
-use energy from ATP
-is a protein
-assists protein folding
-excludes water so it doesn’t affect protein shape
-heat shock proteins:
produced by cell sunder stress
many members are chaperones
-barrel shaped
describe quaternary structure
Association of individual polypeptide subunits (dimers, tetramers, oligomers e.g. F-actin)
Forms one functional protein (non-covalent)
Subunits can be the same (homo) or different (hetero)
Increases stability
describe the changing structure of Hb
-allosteric so binding site changes
-conformation change occurs in response to oxygen binding
-cooperative binding of oxygen
describe protein ‘switches’
-GTPase family: guanine nucleotide dependent regulatory switches e.g. Ras, G proteins
-Active conformation when bound to GTP
-When bound to GDP activity turned off
Ras:
Controls cell growth
Commonly mutated in cancer
why is shape important for enzymes ?
-active site of enzyme is specific to shape of substrate and bonds that can be formed
-antibodies have to bind to specific antigens
why do most enzymes need a metal ion?
so electrostatic forces of attraction can form
what is protein denaturation?
conformation of a protein changing bc the bonds have been disrupted and thus it has lost its function
what are causes of denaturation?
-change in pH
-change in temp
-acids
-bases
-high salt conc
-solvent
how can protein folding cause disease?
-aggregation of misfolded proteins
-amyloid related diseases are Alzheimer’s, Parkinson’s and Huntington’s -tightly packed layers of stable beta sheets
what is a therapeutic approach for diseases caused by protein misfolding?
pharmaceutical chaperones that can fold proteins back into original shape
what are prions?
misfolded proteins that can transmit their misfolded shape on to normal variants of the same protein
what are diseases related to prions?
-CJD (Creutzfeldt-Jakob disease)
-BSE (Bovine Spongiform Encephalopathy)
why can prions not be sterilised?
because they are not organisms so they will not be killed
how do prions lead to neurodegeneration?
form deposits in the brain
how do prions induce misfolding?
they act as templates and increase b pleated sheets
describe the acidic amino acids
-carboxyl group is deprotonated
-negatively charged at neutral pH
-forms electrostatic interactions
-e.g. aspartate, glutamate
describe basic amino acids
-positively charged at neutral pH
-hydrophilic nitrogenous bases
-e.g. histidine, lysine, arginine
