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Published online 24 July 2000. doi:10.1083/jcb.150.2.349
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© The Rockefeller University Press, 0021-9525/2000//349 $5.00
The Journal of Cell Biology, Volume 150, Number 2, , 2000 349-360

Original Article

HIV-1 Rev Depolymerizes Microtubules to Form Stable Bilayered Rings



Norman R. Wattsa,b, Dan L. Sackettc, Rita D. Wardd, Mill W. Millere, Paul T. Wingfieldb, Stephen S. Stahlb, and Alasdair C. Stevena

a Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases,
b Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases,
c Laboratory of Integrative and Medical Biophysics, National Institute of Child Health and Human Development
d Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892
e Department of Biological Sciences, Wright State University, Dayton, Ohio 45435
Laboratory of Integrative and Medical Biophysics, NICHD/NIH, Bldg. 12A, Rm. 2041, Bethesda, MD 20892-5626.(301) 496-2172(301) 594-0358

sackettd{at}mail.nih.gov

We describe a novel interaction between HIV-1 Rev and microtubules (MTs) that results in the formation of bilayered rings that are 44–49 nm in external diameter, 3.4–4.2 MD (megadaltons) in mass, and have 28-, 30-, or 32-fold symmetry. Ring formation is not sensitive to taxol, colchicine, or microtubule-associated proteins, but requires Mg2+ and is inhibited by maytansine. The interaction involves the NH2-terminal domain of Rev and the face of tubulin exposed on the exterior of the MTs. The NH2-terminal half of Rev has unexpected sequence similarity to the tubulin-binding portion of the catalytic/motor domains of the microtubule-destabilizing Kin I kinesins. We propose a model wherein binding of Rev dimers to MTs at their ends causes segments of two neighboring protofilaments to peel off and close into rings, circumferentially containing 14, 15, or 16 tubulin heterodimers, with Rev bound on the inside. Rev has a strong inhibitory effect on aster formation in Xenopus egg extracts, demonstrating that it can interact with tubulin in the presence of normal levels of cellular constituents. These results suggest that Rev may interact with MTs to induce their destabilization, a proposition consistent with the previously described disruption of MTs after HIV-1 infection.

Key Words: acquired immunodeficiency syndrome • HIV-1 Rev • kinesin • microtubules • tubulin

© 2000 The Rockefeller University Press

Abbreviations used in this paper: MAP, microtubule-associated protein; MD, megadalton; MEM, 100 mM MES, 1 mM EGTA, 1 mM MgCl2, pH 6.9; MT, microtubule; RTT, Rev tubulin toroidal complex; STEM, scanning transmission electron microscope.


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