Transcript Document

Protein Structures
Ramachandran plot
Shows grouping of φψ
combinations and relates
them to structures
in real proteins
Repetitive structures (helices, -sheets) are
common.
-helix
• 3.6 amino acids per turn
• 0.54 nm per turn
• side chains pointed out
• H-bonds parallel to axis
• n-4 H-bonds
• dipole moment (neg. at C end)
• no pro, less gly, ser
• limited similar side chain charges
-helices have a dipole moment
some side chains are preferred
ß-sheets are
parallel
or
anti-parallel
And ß-sheets are “pleated”
ß-sheets can form a “ß-barrel”
A recent paper elucidates the ß-barrel structure of a
toxic amyloid protein
Laganowsky et al., “Atomic view of a toxic amyloid small oligomer”, Science 9 March 2012, 335:1228
A reverse turn (ß-bend):
R2 (C=O side) is often G,A
R3 (N-H side) is often D
Proline is often R2 or R3
Tertiary structure involves bonds between and
among side chains:
…O-)
•Hydrogen (-O-H
•Ionic (generally repulsion: -CH2-NH3+:::::::+H3N-CH2-)
•Van der Waal’s (short distance attraction)
•Disulfide (covalent: -CH2-S-S-CH2-)
•Hydrophobic
The types of side chains, and the tertiary bonds they form,
influence the positions of secondary structures.
And the position of a secondary structure in a protein will
influence the types of side chains (tertiary structure).
An -helix on the surface of a protein will have hydrophilic side chains
on one side of the helix axis and hydrophobic side chains on the other.
An -helix in the interior of a protein will have primarily hydrophobic side chains.
An -helix exposed to the solution on all sides (unusual) will have
hydrophilic side chains on all sides of the helix axis (mostly).
Quaternary structures Involve
separate polypeptides held together
with weak bonds in various
symmetries
Symmetries
Homomultimer::
heteromultimer
Isologous::
heterologous
Closed::open
E.g.: tubulin, actin, TMV coat
E.g.: hemoglobin
Secondary-tertiary structure of UVR8 subunits involves multiple ß-sheets.
Quaternary structure involves electrostatic interactions between positively
charged arginines and negatively charged aspartates.
The folding of a protein reduces the free energy (G) of the system.
Folding states
The folding of a protein involves both protein and solvent.
G = GF- GU
= H - TS
=
+ H(protein)
+ H(solvent)
-- TS(protein)
-- TS(solvent)
G for folding
is small (-20 to
-60 kJ/mol) and
primarily from
hydrophobic
interactions
Why so low?
Changes in shape are an important part of protein function and control.
For example: a change in shape allows DNA methyltransferase
to choose hemi-methylated meCG/GC for bimethylation to meCG/GmeC
Science 25 Feb 2011: Song, et al., 331:1036
Summary:
Primary structure involves bonds between amino and carboxylic
groups, stabilizing the amino acid sequence
Secondary structure involves hydrogen bonds between backbone atoms, forming -helices, ß-sheets, and ß-bends.
Tertiary structure involves bonds between side chains.
Quaternary structure involves bonds connecting separate polypeptide chains.
G for folding is small and primarily from hydrophobic interactions.
Stigler et al., The complex folding network of single calmodulin molecules.
Science 334:512, 28 October 2011
Lindorff-Larsen et al., How fast-folding proteins fold. Science 334:517,
28 October 2011
Dill and MacCallum, The protein-folding problem, 50 years on. Science
338:1042, 23 November 2012
Saibil, Machinery to reverse irreversible aggregates. Science 339:1040,
1080 March 2013