William Wedemeyer
Assistant Professor
- Ph.D. 1998, Cornell University
- Postdoctoral Fellow 1998-2001, Cornell University
- Postdoctoral Fellow 2001-2003, University of Washington, Seattle
proteins@msu.edu
509 Biochemistry Building
Michigan State University
East Lansing, MI 48824-1319
Office: 517-355-6490
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William Wedemeyer Research Interests continued
Conformational Changes in gp120 During HIV-1 Cell Entry (continued)
We hypothesize that gp120 avoids neutralization by cloaking the structures needed for infection until the moment of infection. gp120 undergoes at least two major conformational changes during viral entry, the first upon binding to CD4 (its receptor on the target cell) and the second upon binding to a cellular chemokine receptor (either CCR5 or CXCR4). These conformational changes in gp120 may produce the structures needed for infection, either (1) by uncovering pre-formed but buried structures or (2) by folding those structures from a disordered or differently folded conformation. Unfortunately, these conformational changes are poorly understood, since gp120 is difficult to crystallize and too large (approx. 477 residues) for traditional NMR.
We are tackling this problem by combining de novo protein-structure prediction methods with medium-resolution structural probes, including 19F NMR, fluorescence, chemical modification, and proteolysis. Our gp120 comes from a primary isolate of clade A2 HIV-1, and has been cloned and expressed in mammalian and insect expression systems. Virological experiments are being carried out in parallel by our collaborator, Mary Poss.
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