gly

Chymotrypsin (247 aa)

Conformation: the spatial arrangement of atoms in a protein.

Among the many conformations that are theoretically possible in a
protein, one (or a few) conformation exists in biological system.
Native conformation: the conformation of the functionally active
protein.

Levels of structure in proteins

The primary structure describes mainly the

sequence of amino acid residues in the
polypeptide chain. It describes all covalent
bonds (peptide bonds and disulfide bonds)
linking amino acid residues in a polypeptide
chain.
A chain

B chain

Secondary structure refers to particularly stable

arrangements of amino acid residues, near one
another in the linear sequence (primary
structure). These spatial arrangements are local
and give rise to regular repeating structures.
Most important secondary structures are:
helix
sheet
turn
loop

Hydrogen bonding for an helix involve N-H and C=O

groups of peptide bonds

The CO group of residue i forms a hydrogen bond with the

NH group of residue i + 4
http://www.youtube.com/watch?v=eUS6CEn4GSA&feature=related

Structure of a strand

amino acid residues are almost completely extended;

the distance between two adjacent residues is 3.5 ;
the side chains of adjacent residues point in opposite directions.

Antiparallel sheet: adjacent strands run

in opposite directions

Hydrogen bonds connect each amino acid on one strand

to a single amino acid on the adjacent strand.

Parallel sheet: adjacent strands run in the same

direction

Hydrogen bonds connect each amino acid on one strand

with two different amino acid on the adjacent strand.
http://www.youtube.com/watch?v=wM2LWCTWlrE&NR=1

Connections between adjacent strands in sheets

D. Voet, J.G. Voet, C.W. Pratt, FONDAMENTI

DI BIOCHIMICA 2/E, Zanichelli Editore
S.p.A. Copyright 2007

 turns: connecting elements linking secondary structures

A peptide bond involving proline in the

cis configuration is prone to a tight turn.

X-ray structure of carboxypeptidase A

Loops do not have regular, periodic structures

Figure 6-12

The tertiary structure refers to the overall

three dimensional arrangement of all atoms
in a protein.
It is the three dimensional structure of the
functionally active protein (native
conformation).

Based on tertiary structure, proteins are grouped in:

fibrous proteins
globular proteins
shape:

one preferred direction

spherical, globular

secondary structures:

single (few) type(s)

several types

water solubility:

insoluble

soluble

sensitivity to proteases:

very low

high

function:

structural

dynamic

examples:

collagen, keratin,
elastin

enzymes,
immunoglobulins,
some hormones,
hemoglobin

Leucine zipper
Berg et al., BIOCHIMICA 6/E, Zanichelli
editore S.p.A. Copyright 2007

Globular proteins are compact structures

(human serum albumin 585 res.)

Tertiary structure of myoglobin (153 res.)

Myoglobin

three dimensional view

Yellow: hydrophobic amino acids
Blue: charged amino acids
White: other amino acid.

cross sectional view

In globular proteins amino acid residues are distributed

according to the polarity of their side chains:
in the protein core, buried to the solvent: Val, Leu,
Ile, Met and Phe;
on the protein surface interacting with the solvent:
Arg, His, Lys, Asp, Glu;
on the protein surface, but also inside: Ser, Thr, Asn,
Gln, Tyr.

Supersecondary structures (motifs):

combinations of secondary structural elements.

motif

hairpin
motif

motif

Domains :
a) distinct structural units of a polypeptide;
b) may fold as independent compact units.
They maintain their structure when
separated from the rest of the protein (i.e.
by proteolysis);
c) may have separate functions (i.e. binding
of small molecules, interaction with other
proteins).

Glyceraldehyde-3phosphate
dehydrogenase
in red: domain that bind
NAD
in green: domain that
bind glyceraldehyde-3phosphate

D. Voet, J.G. Voet, C.W. Pratt, FONDAMENTI

DI BIOCHIMICA 2/E, Zanichelli Editore
S.p.A. Copyright 2007

Quaternary structure: the three-dimensional

structure of a multi-subunit protein and how the
subunits fit together.