Multidomain proteins properties

As most NRPS multienzymes are multidomain proteins with multiple activation domains, multiple sites may participate in the reactions assayed, and no clear result concerning a single specific site may result. In ACV synthetases, the nonadditivity of the initial rates has been observed in the S. clavuligerus enzyme [35] and the A. chrysogenum enzyme [1]. Two or more site activations of one substrate amino acid could be expected to depend on different binding constants, and thus be detectable by kinetic analysis. So far, however, no evidence for mixed types of concentration dependence has been found. It is thus not yet clear if nonadditivity results from misactivation or alteration of kinetic properties in the presence of multiple substrates. In the case of gramicidin S synthetase 2, evidence for misactivations has been reported [59],... 

These results demonstrate that, in analogy to the multidomain proteins in biosili-cification, triblock copolymers can direct the assembly of silica into complex structures. Furthermore, combining complex ABC copolymer architectures with the physical, electrical, and optical properties of inorganic materials holds considerable... 

Multidomain proteins may be viewed as conjugated proteins in which each domain may affect the folding dynamics and thermodynamic properties of its counterpart domain. Experimentally, the thermodynamics and kinetics of both isolated domains and conjugated constructs from several multidomain proteins were studied (a very detailed and fairly current report can be found in Reference [29]). A computational characterization of the mechanistic principles of the folding of multidomain proteins [33], utilizing native structure-based models, provides a reduced microscopic description of their folding, which in turn may enable the formulation of the forces involved in the interplay between neighboring domains. 

The domain hypothesis (Edelman, 1970) states that the single polypeptide chain in a multidomain protein was formed by gene fusion or gene duplication. As a consequence, one should expect different functional properties to be associated to the different domains. Continuous domains result from gene fusion and discontinuous domains from gene insertion (Janin, 1979) (Fig. 2.49). 

The Ca2+-dependent neutral proteases called calpains are found within the cells of higher animals. The 705-residue multidomain peptide chain of a chicken calpain contains a papain-like domain as well as a calmodulin-like domain.328 It presumably arose from fusion of the genes of these proteins. At least six calpains with similar properties are known.329 Some have a preference for myofibrillar proteins or neurofilaments.330 They presumably function in normal turnover of these proteins and may play a role in numerous calcium-activated cellular processes.331-3323... 

Perlecan, the major secreted proteoglycan in basal laminae, consists of a large multidomain core protein ( 400 kDa) with three or four specialized GAG chains. Both the protein and the GAG components of perlecan contribute to its ability to incorporate into and define the structure and function of basal laminae. Because of Its multiple domains with distinctive binding properties, perlecan can cross-link not only ECM components to one another but also certain cell-surface molecules to ECM components. 

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