TY - JOUR
T1 - Structure of Epstein-Barr Virus Glycoprotein 42 Suggests a Mechanism for Triggering Receptor-Activated Virus Entry
AU - Kirschner, Austin N.
AU - Sorem, Jessica
AU - Longnecker, Richard
AU - Jardetzky, Theodore S.
N1 - Funding Information:
The authors would like to thank Beth Wurzburg, Jacob P. Keller, Marija Backovic, and other members of the Jardetzky and Longnecker laboratories for helpful discussions. The authors thank Jaime Schneider for assistance with protein handling and initial crystallization trials. The authors thank Zdzislaw Warwzak for assistance at beamlines 5-ID (Dupont-Northwestern-Dow Collaborative Access Team) and 21-ID (Life Sciences Collaborative Access Team) of the Advanced Photon Source, which were used to collect X-ray data for screening gp42 crystals. Data published in this manuscript were collected at beamline 22-ID (Southeast Regional Collaborative Access Team), with appreciation for assistance by Gregory Sahli. A.N.K. was supported in part by a predoctoral fellowship from Northwestern's Biotechnology Training Program from the National Institutes of Health and by Northwestern's Medical Scientist Training Program (5 T32 GM008152). J.S. was supported by the Training Program in Viral Replication (NIH T32 AI060523). This work was supported by Public Health Service grants CA93444 and CA117794 from the National Cancer Institute (T.S.J. and R.L.).
PY - 2009/2/13
Y1 - 2009/2/13
N2 - Epstein-Barr virus requires glycoproteins gH/gL, gB, and gp42 to fuse its lipid envelope with B cells. Gp42 is a type II membrane protein consisting of a flexible N-terminal region, which binds gH/gL, and a C-terminal lectin-like domain that binds to the B-cell entry receptor human leukocyte antigen (HLA) class II. Gp42 triggers membrane fusion after HLA binding, a process that requires simultaneous binding to gH/gL and a functional hydrophobic pocket in the lectin domain adjacent to the HLA binding site. Here we present the structure of gp42 in its unbound form. Comparisons to the previously determined structure of a gp42:HLA complex reveals additional N-terminal residues forming part of the gH/gL binding site and structural changes in the receptor binding domain. Although the core of the lectin domain remains similar, significant shifts in two loops and an α helix bordering the essential hydrophobic pocket suggest a structural mechanism for triggering fusion.
AB - Epstein-Barr virus requires glycoproteins gH/gL, gB, and gp42 to fuse its lipid envelope with B cells. Gp42 is a type II membrane protein consisting of a flexible N-terminal region, which binds gH/gL, and a C-terminal lectin-like domain that binds to the B-cell entry receptor human leukocyte antigen (HLA) class II. Gp42 triggers membrane fusion after HLA binding, a process that requires simultaneous binding to gH/gL and a functional hydrophobic pocket in the lectin domain adjacent to the HLA binding site. Here we present the structure of gp42 in its unbound form. Comparisons to the previously determined structure of a gp42:HLA complex reveals additional N-terminal residues forming part of the gH/gL binding site and structural changes in the receptor binding domain. Although the core of the lectin domain remains similar, significant shifts in two loops and an α helix bordering the essential hydrophobic pocket suggest a structural mechanism for triggering fusion.
KW - MICROBIO
KW - PROTEINS
UR - http://www.scopus.com/inward/record.url?scp=59649122639&partnerID=8YFLogxK
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U2 - 10.1016/j.str.2008.12.010
DO - 10.1016/j.str.2008.12.010
M3 - Article
C2 - 19217393
AN - SCOPUS:59649122639
SN - 0969-2126
VL - 17
SP - 223
EP - 233
JO - Structure
JF - Structure
IS - 2
ER -