Molecular Mimicry: Structural and Physiological Investigations

Introduction Independent molecules are expected to possess distinct three-dimensional structures. However, it is becoming increasingly evident that diverse biological molecules, particularly proteins, do not have entirely unrelated structural architectures, even when their functions are independent. It is apparent that the protein structural repertoire is generated from a finite number of structural modules which are used again and again in different contexts and combinations [Chothia and Finkelstein, 1990; Murzin and Chothia, 1992; Chavali et al., 2001]. Many such structural modules have been identified and many more might emerge [Efimov, 1997; Chavali et al., 1997]. Nevertheless, it is likely to be still a finite number. The structural redundancy associated with the protein architecture on one hand and the commonality in the nature of interactions defining specificity of recognition on the other, could lead to the failure in the specificity of molecular communication. Molecular mimicry, in essence, is a consequence of such a failure in the specificity of molecular recognition. In the physiological context, molecular mimicry is manifested in a variety of ways. The accidental structural resemblances between unrelated molecules can have functional implications [Baum et al., 1993]. Molecular mimicry also occurs by design in various regulatory mechanisms [Bode and Huber, 1992; Kobe and Deisenhofer, 1996]. It has implications in rational drug design as well [Beeley, 1994; Tian et al., 1998]. Focus of research in this laboratory, over past several years, has been to exploit x-ray crystallography along with biochemical approaches towards understanding the structural basis of molecular mimicry.