Protein Structure Flashcards
Units, peptide bond, amino acid residue bonds, alpha helix, beta sheet, reverse turn, loops, tertiary structure, common folds, quaternary structure.
What is Å?
Angstrom
1Å = 1 x 10^-10 m (0.1 nm)
How long is a peptide bond?
1.32 Å
CN single bond = 1.49 Å
CN double bond = 1.27 Å
What is Da?
Dalton - unit of atomic mass very nearly equal to that of a hydrogen atom.
Used to express mass on the atomic scale of objects.
Used for protein molecular weight.
1 kDa = 1000 Da
What makes planar peptide bonds stronger and less flexible?
Peptide bond has partial double bond character.
List the 2 possible configurations for the planar peptide bond.
Trans-configuration.
Cis-configuration.
What is a trans-configuration in terms of the planar peptide bond?
2 alpha carbons on opposite sides of peptide bond.
What is a cis-configuration in terms of the planar peptide bond?
2 alpha carbons on same side of peptide bond.
What configuration are most peptide bonds? Why?
Trans-configuration:
R-groups are on opposite sides of the chain to avoid steric (atoms in space) clashes.
What is the exception to this?
Proline can be in cis configuration.
Where does protein flexibility come from?
Free rotation around single bonds in a residue (the structure of each residue can be adjusted).
What is Phi (Φ)?
The angle of rotation about bond between N and alpha C atom.
What is Psi (Ψ)?
The angle of rotation about bond between alpha C atom and carbonyl C atom.
The angles Φ and Ψ determine…
The path of the polypeptide chain (where it will fold).
In 1963, Gopalasamudram N. Ramachandran and his co-workers recognised many combinations of phi and psi were forbidden due to…
(If confused look at PowerPoint).
steric collisions between atoms.
Allowed values are visualised on a 2D…
(If confused look at PowerPoint).
Ramachandran plot (scale = 180 on both ends).
Top left corner = beta strands
Top right corner = left handed alpha helix
Middle left = right handed alpha helix
What is it that limits the number of structures accessible to the unfolded polypeptide chain?
- Rigidity of peptide bond.
- Restricted set of allowed phi and psi
angles.
What are the secondary structures available to the polypeptide chain?
Alpha helices
Beta sheets
Reverse turns
Omega loops
What is an alpha helix?
A rod-like structure consisting of a tightly coiled polypeptide chain which forms the inner part of the tube and amino acid residue groups extend outwards in a helical array.
How many residues (n) per turn are there?
(If confused look at PowerPoint).
3.6
Give the pitch distance of an alpha helix.
Pitch distance = the distance the helix rises along its axis/turn.
5.4 Å
How does hydrogen bonding affect the structure of an alpha helix?
Stabilises the structure - the bond is almost at optimal length (2.8 Å).
How many residues is an alpha helix?
Vary from 4-40 residues.
Average length of globular proteins = 10.
How is hydrogen bonding arranged in an alpha helix?
So peptide C=O group of residue n points along helix towards peptide N-H group of residue n + 4.
How many amino acid residues are there between 2 groups making up a hydrogen bond?
3
What is a helical wheel?
(Look at PowerPoint if confused).
The view of the alpha helix from above.
Since one turn of an alpha helix is 3.6 residues long, how can each residue be plotted on a helical wheel?
360/3.6 = 100 degrees around a circle/spiral.
What do helical wheel plots highlight?
Properties of alpha helices in regard to type of amino acid residue R-groups.
Where are amino acids that form polar bonds most likely to be?
On the surface of the protein.
How does the alpha helical content of proteins vary?
From 0% to 100%.
What percentage of all soluble proteins are composed of alpha helices?
25%
What percentage of residues in iron storage protein (ferritin) are alpha helices?
75%
What is the form of the polypeptide chain in a beta-sheet/beta-strand?
It is almost fully extended.
A beta-strand is rarely found in…
Isolation.
How many polypeptide chains are beta sheets?
At least 2 but typically 4/5.
Beta strands come together in beta sheets, there can be 10 or more.
How are beta strands arranged? How do they appear?
Parallel/antiparallel/mixed.
Rippled/pleated appearance.
What is the distance between adjacent amino acid residues in a beta-strand?
3.5 Å
What does hydrogen bonding do for a beta sheet?
Stabilises the sheet.
How many residues are beta strands typically?
3-10 residues long.
When does hydrogen bonding occur in a beta sheet?
Between C=O of one strand to N-H of adjacent strand.
Pattern varies depending on whether adjacent strands are parallel /antiparallel.
How are beta strands depicted?
As broad arrows pointing in C-terminal end direction.
Beta sheets are important structural elements in many proteins, specifically…
fatty acid binding proteins.
What is a reverse turn also known as?
A beta-turn / a hairpin turn.
What stabilises the abrupt changes in direction of the polypeptide chains in beta-sheets?
Hydrogen bonding.
How do hydrogen bonds form reverse turns?
The C=O group of residue i of the polypeptide is hydrogen bonded to the N-H group of residue i + 3.
What are omega loops also known as?
Ω-loops
Unlike alpha helices and beta sheets, omega loops don’t have a structure that is…
regular and periodic.
What are the structures of omega loops often like?
Rigid and well defined.
Why do turns and loops often lie on the surfaces of proteins?
They participate in interactions with other proteins/molecules.
What do elements of the secondary structure do with each other?
Link together into combinations that are very common, these form as motifs that have some stability in their own right.
Motif = specific structural patterns within proteins that are evolutionarily conserved and have particular functions or roles.
List some common motifs.
(If confused, look at PowerPoint).
Helix-turn-helix motif
Hairpin motif
Greek key motif
Beta-alpha-beta motif
What is the tertiary structure? What is it made up of?
The overall fold of the whole protein.
Any combination of alpha helices, beta sheets and omega loops.
What should be done after the formation of the tertiary structure to obtain the active form of the protein/enzyme?
Post-translational modifications and/or binding of co-factors.
Approximately 70% of the main chain is folded into 8 alpha helices. What does the rest form?
Loops and turns.
Myoglobin is a single polypeptide chain of 153 amino acids. It’s overall dimensions are 45x35x25 Å.
What does the polypeptide chain bind to?
A prosthetic haem group.
Prosthetic group = non-peptide compounds that mostly attach to proteins and assist them in different ways.
What did Kendrew and his co-workers publish in 1958?
The first protein structure to be determined = myoglobin.
Each type of representation of a protein highlights different features.
List 3 ways proteins can be represented.
- Ribbon/cartoon diagram.
- Wireframe/ball and stick diagram.
- Space filling models (show surface
residues and cross section shows core
residues).
Concanavalin (Con A) is a lectin that has a tertiary structure of 14 beta-strands. It is an all beta-sheet protein.
What is a lectin?
Carbohydrate binding protein.
Instead of being an all alpha helix or beta sheet protein, what are most proteins?
Mixtures of alpha helices and beta sheets.
List three common tertiary structure folds.
(If confused look at PowerPoint).
Globin fold
Alpha/beta barrel
Beta barrel
All proteins fold into at least one…
domain.
Many proteins have several sections that fold independently to form domains.
What is a domain?
A region of polypeptide chain that is distinct, independently folding and region is self-stabilising.
But some have many for example more than…
10.
How do domains range in size?
From 30-400 amin acid residues.
What is the quaternary structure of a protein?
Groups of 2 or more polypeptide chains.
Homomultimer = a protein with two or more copies of the same protein monomer/subunits.
Heteromultimer = a mature protein with several different protein monomers/subunits.
Haemoglobin is a tetramer comprised of two pairs of slightly dissimilar subunits (α2β2).
What is a tetramer?
Polymer with 4 subunits.
Each subunit binds to a haem group, so how many oxygen molecules can haemoglobin transport?
4.
What is a multimeric protein?
A protein composed of several subunits.
Define protein.
Formed from polypeptide chain(s) of 50-2000 amino acid residues.
The molecular weight of most proteins is between 5500 and 220,000 Da.
Proteins are on the nanometre scale and their widths range 2-100nm.
Titin is an exception of this.
The muscle protein is 34,000 amino acids.
The molecular weight 3,816,030 Da.
The length stetches up to 1.5 micro metres.
