Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 426, Issue 5, Pages 1077-1094Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2013.11.010
Keywords
HIV; gp41; structure; fusion peptide; NMR
Categories
Funding
- National Institutes of Health [R01A1047153, F32A1080136]
- Israel Science Foundation
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The HIV gp41 protein catalyzes fusion between viral and, target cell membranes. Although the 20-residue N-terminal fusion peptide (FP) region is critical for fusion, the structure of this region is not well characterized in large gp41 constructs that model the gp41 state at different times during fusion. This paper describes solid-state NMR (SSNMR) studies of FP structure in a membrane-associated construct (FP-Hairpin), which likely models the final fusion state thought to be thermostable trimers with six-helix bundle structure in the region C-terminal of the FP. The SSNMR data show that there are populations of FP-Hairpin with either a helical or 13 sheet FP conformation. For the 13 sheet population, measurements of intermolecular 13C-13C proximities in the FP are consistent with a significant fraction of intermolecular antiparalle113 sheet FP structure with adjacent strand crossing near L7 and F8. There appears to be negligible in-register parallel structure. These findings support assembly of membrane-associated gp41 trimers through interleaving of N-terminal FPs from different trinners. Similar SSNMR data are obtained for FP-Hairpin and a construct containing the 70 N-terminal residues of gp41 (N70), which is a model for part of the putative pre-hairpin intermediate state of gp41. FP assembly may therefore occur at an early fusion stage. On a more fundamental level, similar SSNMR data are obtained for FP-Hairpin and a construct containing the 34 N-terminal gp41 residues (FP34) and support the hypothesis that the.FP is an autonomous folding domain. (C) 2013 Elsevier Ltd. All rights reserved.
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