a surface groove essential for viral bcl-2 function during chronic infection in vivo表面槽必不可少的病毒bcl - 2在慢性感染体内功能.pdfVIP

A Surface Groove Essential for Viral Bcl-2 Function During Chronic Infection In Vivo 1[a 2[a 2 2 3 4 Joy Loh , Qiulong Huang , Andrew M. Petros , David Nettesheim , Linda F. van Dyk , Lucia Labrada , 5 6 2[b 1[b* Samuel H. Speck , Beth Levine , Edward T. Olejniczak , Herbert W. Virgin IV 1 Departments of Pathology and Immunology and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America, 2 Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois, United States of America, 3 Department of Microbiology, University of Colorado Health Science Center, Aurora, Colorado, United States of America, 4 Department of Medicine, Columbia College of Physicians and Surgeons, New York, New York, United States of America, 5 Division of Microbiology and Immunology, Yerkes Regional Primate Center, Emory University, Atlanta, Georgia, United States of America, 6 Departments of Internal Medicine and Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America Antiapoptotic Bcl-2 family proteins inhibit apoptosis in cultured cells by binding BH3 domains of proapoptotic Bcl-2 family members via a hydrophobic BH3 binding groove on the protein surface. We investigated the physiological importance of the BH3 binding groove of an antiapoptotic Bcl-2 protein in mammals in vivo by analyzing a viral Bcl-2 family protein. We show that the c-herpesvirus 68 (cHV68) Bcl-2 family protein (cHV68 v-Bcl-2), which is known to inhibit apoptosis in cultured cells, inhibits both apoptosis in primary lymphocytes and Bax toxicity in yeast. Nuclear