Domains in Proteins

Index to Course Material Index to Section 10 Identification References

DOMAIN MOVEMENTS

Protein flexibility is demonstrated by large relative movements of domains, for example, in aspartic proteinases the two lobes have large relative shifts as identified by Sali et al., (1992). Such motions are important for functions like catalysis, ligand binding, regulation of activity, formation of protein assemblies and transport of metabolites. Often the domains constitute a binding site at the interface wherein closed conformations of domains correspond to inactive form of the enzyme while open conformations of domains correspond to the active form of the enzyme, illustrating induced fit in recognition (Koshland, 1958).

Mechansisms of domain movements -

1. Intrinsic flexibility -
   Several small movements in secondary structures which has a cummulative effect. This may be further classified into two types:

   • (a) movements not constrained by packing interactions like those involving hinge motions in strands and helices. This may be slight deformations in backbone torsion angles of strands/helices (for example strand movements in lactoferrin, helix deformation in lactate dehydrogenase from an alpha-helix to 3(10) helix (Gerstein & Chothia, 1991), kinks involving prolines in helices as in adenylate kinase (Gerstein et al., 1994), interconversion of helix and extended conformations as in calmodulin (Ikura et al. 1992) and in triglyceride lipase (Derewande et al., 1992)).
   • (b) shear movements at the domain interface which are constrained by packing interactions. The domain movements may be perpendicular or parallel to the interface between the domains. If it is parallel, the movements are largely due to small sidechain torsion angle changes often within the same preferred ranges (for example domain movements in citrate synthases (Remington et al., 1982) between the small and large domains is by side chain movements in residues in pairs of packed helices). An example of movements perpendicular to the domain interface is observe in aspartyl aminotransferase (McPhalen et al., 1992).

2. Hinged domain movements -
   In order that each subunit in the tobacco bushy stunt virus fits into the icosahedral symmetry, the S and P domains undergo displacements mainly by the change in conformation of the peptide that forms a linker between the two (Olsen et al., 1983). On the other hand in the transport proteins like lactoferrin, the open and closed forms of the two domains involve a 53 degree rotation which is achieved by two strands that connect two domains (Anderson et al., 1990). More complex hinge motions take place in protein kinase (Knighton et al., 1991) and in adenylate kinases (Berry et al., 1994).

3. Ball-and-socket motion -
   The variable (light and heavy chain) domains of antibodies rotate about 50 degrees with respect to the heavy (light and heavy chain) by means of a combination of hinge and shear motions (Lesk and Chothia, 1988).

Index to Course Material

Index to Section 10

Identification

References

Last updated 11th Jun '96