Insilico structural analysis of an immunotherapeutic glycoprotein t11ts (sheep cd58)

Authors:Sirshendu Chatterjee, Aparna Laskar, Ananya Chatterjee, Chhabinath Mandal, Swapna Chaudhuri
Int J Biol Med Res. 2011; 2(1): 346- 359  |  PDF File

Abstract

T11-Target Structure (T11TS) is a 42 K SRBC membrane glycoprotein and the classical ligand of the E-receptor (CD2). It is an important costimulator of T cell activation process. Therapeutic potential of the bioactive molecule has recently been deciphered and thus necessitated structural analysis. 3D structure of extracellular domain (residues 2-192) of T11TS was generated using 1CCZ_A as template by web based molecular modeling program ‘LOOPP’ and refined by energy minimization (SD and CG) and molecular dynamics simulations in cff91.frc force field. Structural quality assessment of the final model with six high throughput structure validation programs (PROCHECK, MODELYN, MOLPROBITY, VERIFY_3D, ERRAT and PROSA) demonstrated its reliability for further studies. Secondary structural analysis reveals that 41.36%, 21.99%, 3.66%, 3.14% and 29.84% residues of the final model form β-sheet, bend, turn, 310 helix and coil conformations respectively. Insilico analysis of the three receptor-ligand complexes viz. T11TS-humanCD2, T11TS-ratCD2 and T11TS-mouseCD2 highlight that the main interacting residues (Met27, Phe29, Lys32, Asp33, Lys34, Glu37, Asp39, Gln40 and Phe47) are highly conserved and located in a heterophilic, charged AGFCC′C″ face on the N-terminal IgV domain of T11TS. Intermolecular hydrogen bonding and electrostatic force play a prominent role in these receptor-ligand interactions. Although the CD2 binding domain contains two potential N-type glycosylation sites (N-12, and N-62) but none is found to be present within 4A0 of the CD2 binding interface, implies their probable functional silence in immune activation process. The phylogenetic analysis using KITSH program shows that T11TS and bovine CD58 is closely related to each other.