complex structure of engineered modular domains defining molecular interaction between icam-1 and integrin lfa-1复杂的结构设计模块化的域定义icam-1之间的分子间相互作用和整合素lfa-1.pdf

Complex Structure of Engineered Modular Domains Defining Molecular Interaction between ICAM-1 and Integrin LFA-1 1 2 1 1 1 Sungkwon Kang , Chae Un Kim , Xiaoling Gu , Roisin M. Owens , Sarah J. van Rijn , 1 3 4 1 Vanissra Boonyaleepun , Yuxin Mao , Timothy A. Springer , Moonsoo M. Jin * 1 Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America, 2 Cornell High Energy Synchrotron Source, Cornell University, Ithaca, New York, United States of America, 3 Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America, 4 Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America Abstract Intermolecular contacts between integrin LFA-1 (a b ) and ICAM-1 derive solely from the integrin a I domain and the first L 2 L domain (D1) of ICAM-1. This study presents a crystal structure of the engineered complex of the aL I domain and ICAM-1 D1. Previously, we engineered the I domain for high affinity by point mutations that were identified by a directed evolution approach. In order to examine aL I domain allostery between the C-terminal a7-helix (allosteric site) and the metal-ion dependent adhesion site (active site), we have chosen a high affinity variant without mutations directly influencing either the position of the a7-helix or the active site