Alternative intermolecular contacts underlie the rotavirus VP5* two- to three-fold rearrangement

The EMBO Journal
Joshua D Yoder, Philip R Dormitzer

Abstract

The spike protein VP4 is a key component of the membrane penetration apparatus of rotavirus, a nonenveloped virus that causes childhood gastroenteritis. Trypsin cleavage of VP4 produces a fragment, VP5*, with a potential membrane interaction region, and primes rotavirus for cell entry. During entry, the part of VP5* that protrudes from the virus folds back on itself and reorganizes from a local dimer to a trimer. Here, we report that a globular domain of VP5*, the VP5* antigen domain, is an autonomously folding unit that alternatively forms well-ordered dimers and trimers. Because the domain contains heterotypic neutralizing epitopes and is soluble when expressed directly, it is a promising potential subunit vaccine component. X-ray crystal structures show that the dimer resembles the spike body on trypsin-primed virions, and the trimer resembles the folded-back form of the spike. The same structural elements pack differently to form key intermolecular contacts in both oligomers. The intrinsic molecular property of alternatively forming dimers and trimers facilitates the VP5* reorganization, which is thought to mediate membrane penetration during cell entry.

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Citations

Feb 13, 2008·Expert Reviews in Molecular Medicine·Richard L Ward
Jun 16, 2007·Nature Reviews. Microbiology·Juana AngelHarry B Greenberg
Dec 9, 2010·The Journal of Biological Chemistry·Fiona E FlemingBarbara S Coulson
Aug 21, 2009·Journal of Virology·Joshua D YoderPhilip R Dormitzer
Sep 15, 2006·Journal of Virology·Shane D Trask, Philip R Dormitzer
Dec 17, 2009·Journal of Virology·Shane D TraskPhilip R Dormitzer
Nov 28, 2008·Journal of Virology·Zongli LiB V Venkataram Prasad
Apr 9, 2010·Journal of Virology·Irene S KimStephen C Harrison
Nov 4, 2008·Trends in Biotechnology·Philip R DormitzerRino Rappuoli
Dec 16, 2010·The EMBO Journal·Ethan C SettembreStephen C Harrison
Apr 22, 2014·Biochimica Et Biophysica Acta·Sarah ElaidSerge Bouaziz
Oct 11, 2014·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Sunando RoyUNKNOWN New Vaccine Surveillance Network
Sep 12, 2014·PLoS Pathogens·Aliaa H AbdelhakimStephen C Harrison
Dec 9, 2016·Journal of Virology·Melanie H DietrichThilo Stehle
Jan 18, 2020·Virus Evolution·Irene Hoxie, John J Dennehy
Jan 15, 2018·Biochimica Et Biophysica Acta. Biomembranes·Kentaro ShimizuTohru Terada

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