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Beyond Secondary Structure
Supersecondary structure (motifs): small,
discrete, commonly observed aggregates of
secondary structures
 b sheet
 helix-loop-helix
 bab
Domains: independent units of structure
 b barrel
 four-helix bundle
*Domains and motifs sometimes interchanged*
Tertiary Structure
Definition: Overall 3D form of a molecule
 Folding up secondary structures/motifs/domains
 Optimization of interactions between residues
 A specific structure is formed
*All proteins have multiple secondary structures,
almost always multiple motifs, and in some cases
multiple domains*
Tertiary Structure
Specific structures result from long-range interactions
 Electrostatic (charged) interactions
 Hydrogen bonds (OH, N H, S  H)
 Hydrophobic interactions
Soluble proteins have an inside (core) and outside
 Folding driven by water- hydrophilic/phobic
 Side chain properties specify core/exterior
 Some interactions inside, others outside
Tertiary Structure
I. Ionic Interactions (exterior)
Forms between 2 charged side chains:
1 Negative – Glu,Asp, 1 Positive – Lys,Arg,His
 Also called “salt bridges”.
 Ionic interactions are pH-dependent (pKa).
 Occurs at the exterior
 NOTE: pKs for in the interior of a protein may be
very different from free amino acid.
Tertiary Structure
II. Hydrogen bonds
Forms between side chains/backbone/water:
Charged side chains: Glu,Asp,His,Lys,Arg
Polar chains: Ser,Thr,Cys,Asn,Gln,[Tyr,Trp]
 Not a specific covalent bond – lower energy.
 Occurs inside, at the exterior, and with water.
Tertiary Structure
III. Hydrophobic Interactions
Forms between side chains of non-polar residues:
Aliphatic (Ala,Val,Leu,Ile,Pro,Met)
Aromatic (Phe,Trp,[Tyr])
 Clusters of side chains- but no requirement for
a specific orientation like an H-bond
 In the protein interior, away from water
 Not pH dependent
Tertiary Structure
IV. Disulfide Bonds
Forms between Cys residues:
Cys-SH + HS-Cys  Cys-S-S-Cys
 Catalyzed by specific enzymes
 Restricts flexibility of the protein
 Usually within a protein, not for linking proteins