Block B Lecture 1 - Protein Structure Flashcards
What are 3 examples of secondary structures which can appear in a protein?
α-helices
β-turns
β-sheets
(Slide 6)
What stabilises α-helices and β-sheets?
Hydrogen bonding between the coils of the helix / strands of the sheet
(Slide 6)
How can information about what amino acids tend to be in each type of secondary structure be useful?
As it can be used to predict secondary structure from the protein sequence with 60-70% success
(Slide 7)
What is special about arginine in the context of its appearance in secondary structures?
It appears equally in all types of secondary structure
(Slide 7)
What are 3 examples of amino acids which occur in the interior of the protein, away from the aqueous environment?
Answers Include:
Valine, Leucine, Isoleucine, Methionine and phenylalanine
(Slide 8)
What are 3 examples of amino acids which are usually located on the surface of a protein (in contact with the aqueous solvent)?
Answers Include:
Arginine, Histidine, Lysine, Aspartic acid and glutamate
(Slide 8)
What are 3 examples of amino acids which can often be on the surface, but can occur inside the protein if they are hydrogen bonded to something else?
Serine, Threonine, Asparagine and Glutamine
(Slide 8)
What are 2 examples of amino acids which are usually buried, but can occur on the surface of a protein?
Tyrosine and Tryptophan
(Slide 8)
What do amino acids hydropathy scores measure and how are they obtained?
They hydrophobicity of an amino acid residue, and these scores are obtained experimentally
(Slide 9)
Which amino acids have the highest and lowest hydropathy scores?
Isoleucine has the highest (+4.5) and arginine has the lowest (-4.5)
(Slide 9)
What are transmembrane domains usually?
α-helices which are made up of about 20 amino acid residues
(Slide 10)
How can hydropathy values be used to help determine where the transmembrane domain of a protein is?
As a hydropathy plot can be made, where the hydropathy values of each amino acid is plotted. Transmembrane domains are discovered by large (positive) spikes in hydropathy values in the graph.
(Slide 10)
What is bacteriorhodopsin?
A 7TM (7 transmembrane domain) membrane protein found in purple sulphur bacteria which grow in salty conditions.
When nutrients are scarce, these bacteria use bacteriorhodopsin to harvest light energy and use it to make ATP by pumping protons to form a proton gradient
(Slide 11)
What is the “native” structure of a protein?
A structure most proteins have in which they are stable and are to fold spontaneously. This structure is the lowest energy conformation.
(Slide 12)
What are 4 examples of interactions which help stabilise protein structure, and what is the nature of their interaction?
Salt bridges - A noncovalent strong attraction between 2 oppositely charged groups, such as a COO- and NH3+
Van der Waals forces - A noncovalent weak attraction between dipoles on neutral groups. This includes hydrogen bonds.
Hydrophobic interactions - A noncovalent interaction which describes the tendency for nonpolar groups to cluster together away from water
Disulphide bridges - A covalent bonding interaction between the sulphur groups of 2 cysteine amino acids residues which holds different parts of the chain together
(Slide 13)
Rank salt bridges, van der Waal forces, hydrophobic interactions and disulphide bridges on importance in stabilising a protein structure.
Salt bridges - small importance
Van der Waals - quite important due to amount of groups with dipoles
Hydrophobic interactions - very important
Disulphide bridges - important (but mainly for extracellular proteins)
(Slide 13)
Why is the flexibility and movement of proteins essential?
For many functions, namely: enzyme catalysis, recept-ligand binding and signalling and contraction or elasticity in fibrous proteins
(Slide 16)
What can also be contained within tertiary structures?
Motifs / super secondary elements
(Slide 17)
What are motifs?
Recurring combinations of secondary structure elements that form recognizable patterns in proteins. These structures often contribute to a protein’s overall fold and function but are not stable on their own like full tertiary structures. Examples include a helix-loop-helix structure or a zinc-finger
(Slide 17)
What are domains?
They are structurally independent units with the characteristics of small globular proteins. They are about 100-200 residues in size and have independent functions or activities.
Prominent examples are enzymes having a domain to bind its substrate and another to bind NAD+/NADH
(Slide 18)
What is a quaternary structure?
It’s the level above a tertiary structure, and it is the association of 2 or more subunits together to give a multimeric (made up of multiple subunits) protein with its own 3D structure.
(Slide 22)
Can a monomer have a quaternary structure?
No
(Slide 22)
What do multimeric proteins often have?
A line of symmetry, even if they are heteromers
(Slide 24)
What forces drive interactions between subunits?
The same as those present in tertiary structure (i.e salt bridges, hydrophobic interactions and Van der Waal’s forces)
(Slide 25)
How may covalent bonds occasionally form between subunits?
Via salt bridges (2 sulphurs on 2 cysteines binding each other)
Note: in cases where this happens the subunits are unable to dissociate
(Slide 25)
What are 3 advantageous that multimeric proteins (made up of multiple subunits) have?
Large and complex structures can be assembled from simpler units
Binding / catalytic sites can be formed between subunits, resulting in a greater versatility of structure.
The properties of one subunit can be affected by an interaction with another unit, resulting in a mechanism for regulation
(Slide 26)
What are allosteric proteins / enzymes?
Proteins where a ligand binding to one subunit is affected by a ligand binding to another subunit.
Binding of the ligand to a subunit changes it structure and therefore the structure of a adjacent subunit.
This is usually present in cases where a ligand binding to a subunit increases the affinity of the other subunits for the ligand - known as positive co-operativity
(Slide 27)
What is an example of an allosteric protein?
Haemoglobin
(Slide 28)
What is the structure of haemoglobin?
It is an α2β2 tetramer, with each subunit having a heme which binds oxygen
(Slide 28)
What 2 states can haemoglobin subunits be in and what property do these states have?
Tense - low affinity for oxygen
Relaxed - high affinity for oxygen
(Slide 29)
What does binding of oxygen do to the state of the haemoglobin subunit it binds to, and why is this significant?
It changes the state from tense to relaxed, and since all subunits must be in the same state, the other subunits also change to the relaxed state, and is this has a high affinity for oxygen, this allows oxygen to bind to the other subunits
(Slide 29)
How does positive co-operativity affect the ligand binding curve?
It is slower at low oxygen concentrations, but as ligand concentration increases more subunits are put into the relaxed state, greatly increasing infinity
(Slide 30)
What are allosteric effectors?
Ligands which bind to a different site of the enzyme, which is not the catalytic site
(Slide 32)
What is negative allostery?
Opposite of positive co-operativity, where ligand binding decreases affinity for the ligand
(Slide 32)
How do proteins “evolve”?
Motifs, domains and the quaternary structure in proteins facilitate development of diversity and protein families, essentially evolution of function of proteins
(Slide 33)
What are protein families?
A set of proteins which sequence or structural similarities which suggest they are related by evolution.
These structural similarities relate to motif (super secondary) structures and overall 3D organisation
(Slide 34)
What are homologous genes?
Genes which have sequences which share a common evolutionary ancestor
(Slide 35)
What are the 2 subdivisions of homologous gene (+ explain what they are)?
Orthologous genes - genes which have sequences which have a common ancestor which have split due to a speciation event
Paralogous genes - sequences of the descendants of an ancestral gene which has underwent a duplication event
(Slide 35)
How do domains and modules contribute to the evolution of proteins?
Domain recombination and domain-swapping
(Slide 36)
