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.

Chymotrypsin (247 aa)

gly

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

http://www.youtube.com/watch?v=eUS6CEn4GSA&feature=related

The CO group of residue i forms a hydrogen bond with the NH group of residue i + 4

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

D. Voet, J.G. Voet, C.W. Pratt, FONDAMENTI DI BIOCHIMICA 2/E, Zanichelli Editore

S.p.A. Copyright 2007

Connections between adjacent strands in sheets

turns: connecting elements linking secondary structures

A peptide bond involving proline in the cis configuration is prone to a tight turn.

Figure 6-12

X-ray structure of carboxypeptidase A

Loops do not have regular, periodic structures

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, enzymes, elastin immunoglobulins, some hormones, hemoglobin

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

Leucine zipper

Globular proteins are compact structures (human serum albumin 585 res.)

Tertiary structure of myoglobin (153 res.)

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

three dimensional view cross sectional view

Myoglobin

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.

hairpin motif 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).

D. Voet, J.G. Voet, C.W. Pratt, FONDAMENTI DI BIOCHIMICA 2/E, Zanichelli Editore

S.p.A. Copyright 2007

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

Quaternary structure: the three-dimensional structure of a multi-subunit protein and how the subunits fit together.

Diapositiva numero 1Diapositiva numero 2The 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.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.Diapositiva numero 5Diapositiva numero 6Diapositiva numero 7Diapositiva numero 8Diapositiva numero 9Diapositiva numero 10Diapositiva numero 11Diapositiva numero 12The 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).Diapositiva numero 14Diapositiva numero 15Diapositiva numero 16Diapositiva numero 17Diapositiva numero 18Diapositiva numero 19In globular proteins amino acid residues are distributed according to the polarity of their side chains:Diapositiva numero 21Domains : 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).Diapositiva numero 23Diapositiva numero 24