Structural Studies of a New Class of Binding-Proteins Secreted during the Narrow period of Initial Involution

Biophysics, All India Institute of Medical Sciences, New Delhi
○Tej P. Singh Devendra B. Srivastava Janesh Kumar Nagendra Singh Rishi K. Somvanshi Sujata Sharma Sharmistha Dey Asha Bhushan

During the early stage of involution in animals extensive restructuring of the tissue occurs, which includes the elimination of many secretory epithelial cells. However, the molecular processes during this period are very poorly understood. The protein profile of secretions during involution has been studied. It indicated a high concentration of new class 40 kDa glycoproteins. These proteins were designated as signaling proteins (SPX-40). They have been isolated from various animal species such as Human (SPH-40), Bovine (SPC-40), Buffalo (SPB-40), Goat (SPG-40), Sheep (SPS-40) and Camel (SPU-40). The crystal structures of SPX-40 from several species determined at high resolutions revealed that the protein folds into two domains, a large (β/α)8 TIM barrel and a small (α+β). Its overall folding is similar to chitinases but it does not have chitinase activity due to mutations of active site residues. The sugar-binding groove is partly blocked. In order to understand its function, the crystal structures of several complexes with oligosaccharides of different lengths have been determined. Structures of these complexes show large scale conformational changes upon binding to sugars. The structures of SPX-40 also reveal a surface region consisting of three segments with significant disorders and a unique distribution of polar residues suggesting a potential of forming intermolecular interactions. In order to ascertain this aspect, its complexes were co-crystallized with designed peptides. Crystal structures of these complexes revealed that peptides bound to the protein at this site only. Finally, it seems that these proteins are evolved from the family of purely sugar-binding to protein-binding that could retain some sugar-binding capacity.