Comp. by: PG1397SNijam Stage: Revises1 ChapterID: 0001257665APCSB978- 0-12-381262-9 Date:7/4/11 Time:09:56:45 File Path:\\pchns1002z\WOMAT\Production\PRODENV\0000000001\0000025497 \0000000016\0001257665.3d Acronym:APCSB Volume:83006 CORRECTED PROOF c0006 STRUCTURAL DIVERSITY OF CLASS I MHC-LIKE MOLECULES AND ITS IMPLICATIONS IN BINDING SPECIFICITIES By MD. IMTAIYAZ HASSAN AND FAIZAN AHMAD Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India I. Introduction ....................................................................... 224 II. Sequence Analysis .................................................................. 227 A. Ligand-Binding Residues ...................................................... 232 B. TCR-Binding Residues ......................................................... 236 C. Light Chain-Binding Residues ................................................ 238 III. Structure Analysis .................................................................. 239 A. Structure of Ligand-Binding Groove .......................................... 244 B. Structural Basis of TCR Binding .............................................. 251 C. Structural Basis of Light Chain Binding ...................................... 255 IV. Glycosyalation ...................................................................... 258 V. Conclusion ......................................................................... 261 References.......................................................................... 262 Abstract sp0050 The binding groove of class I major histocompatibility complex (MHC) class is essentially important for antigen binding and presentation on T cells. There are several molecules that have analogous conformations to class I MHC. However, they bind specifically to varying types of ligands and cell-surface receptors in order to elicit an immune response. To elucidate how such recognition is achieved in classical MHC-I like mole- cules, we have extensively analyzed the structure of human leukocyte antigen (HLA-1), neonatal Fc receptor (FcRn), hereditary hemochroma- tosis protein (HFE), cluster of differentiation 1 (CD1), gamma delta T cell receptor ligand (22), zinc-a2-glycoprotein (ZAG), and MHC class I chain- related (MIC-A) proteins. All these molecules have analogous structural anatomy, divided into three distinct domains, where a1a2 superdomains form a groove-like structure that potentially bind to certain ligand, while the a3 domain adopts a fold resembling immunoglobulin constant domains, and holds this a1a2 platform and the light chain. We have observed many remarkable features of a1a2 platform, which provide ADVANCES IN PROTEIN CHEMISTRY AND 223 Copyright 2011, Elsevier Inc. STRUCTURAL BIOLOGY, Vol. 83 All rights reserved. DOI: 10.1016/B978-0-12-381262-9.00006-9