Protein Structures

Protein structures
• Prim ary structure(li
nearpolym erofamino acids)
(backbone held tog etherwithpeptide bonds)
• Secondarystructure(standard 3-D pat terns)
( -heli x,ß-sheet,heldtogether withH -bonds
betw een backbone ato m s)
• Tertia ry stru
cture(detail
ed 3-D conform ation)
(bonds betw een side-chain atoms)
• Quaterna ry str
ucture(com bined polym erchains)
(bonds betw een m onom erside-chain ato m s)
Peptide bonds, the basis of primary structure,
also influence secondary structure

Recall that the planar amide bond constrains chain’s

bends

planes: no rotation around CO-N bonds, but planes

rotate around -C-N ( ) and -C-C=O bonds ( )
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:

•Hydrogen (-O-H…O-)

•Ionic (generally repulsion: -CH -NH +:::::::+H N-CH -)

2 3 3 2

•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 back-
bone atoms, forming -helices, ß-sheets, and ß-bends.
Tertiary structure involves bonds between side chains.
Quaternary structure involves bonds connecting separate poly-
peptide 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