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Title: Structures and Polymorphic Interactions of Two Heptad-Repeat Regions of the SARS Virus S2 Protein

Abstract

Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct a-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest a possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
914013
Report Number(s):
BNL-78581-2007-JA
TRN: US0801473
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Structure; Journal Volume: 14; Journal Issue: 5
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; 43 PARTICLE ACCELERATORS; CELL MEMBRANES; CRYSTAL STRUCTURE; GLYCOPROTEINS; MEMBRANES; PROTEINS; TARGETS; THERMODYNAMICS; NSLS; national synchrotron light source

Citation Formats

Deng,Y., Liu, J., Zheng, Q., Yong, W., and Lu, M. Structures and Polymorphic Interactions of Two Heptad-Repeat Regions of the SARS Virus S2 Protein. United States: N. p., 2006. Web. doi:10.1016/j.str.2006.03.007.
Deng,Y., Liu, J., Zheng, Q., Yong, W., & Lu, M. Structures and Polymorphic Interactions of Two Heptad-Repeat Regions of the SARS Virus S2 Protein. United States. doi:10.1016/j.str.2006.03.007.
Deng,Y., Liu, J., Zheng, Q., Yong, W., and Lu, M. Sun . "Structures and Polymorphic Interactions of Two Heptad-Repeat Regions of the SARS Virus S2 Protein". United States. doi:10.1016/j.str.2006.03.007.
@article{osti_914013,
title = {Structures and Polymorphic Interactions of Two Heptad-Repeat Regions of the SARS Virus S2 Protein},
author = {Deng,Y. and Liu, J. and Zheng, Q. and Yong, W. and Lu, M.},
abstractNote = {Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct a-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest a possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.},
doi = {10.1016/j.str.2006.03.007},
journal = {Structure},
number = 5,
volume = 14,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}