DOMAIN MOVEMENTS
This section is largely based on the excellent review by Gerstein et al.
(1994). Mark Gerstein is also largely responsible for
The Protein Motions Database
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 -
-
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).
-
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).
-
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).
R. Sowdhamini 1995
Last updated 7th April '97