@article{c0728e2e40e94f1b956fea9d72845184,
title = "Visualization of the target-membrane-inserted fusion protein of semliki forest virus by combined electron microscopy and crystallography",
abstract = "Semliki Forest virus enters cells by receptor-mediated endocytosis. The acidic environment of the endosome triggers a membrane fusion reaction that is mediated by the E1 glycoprotein. During fusion, E1 rearranges from an E1/E2 heterodimer to a highly stable, membrane-inserted E1 homotrimer (E1HT). In this study, we analyzed E1HT by a combination of electron cryomicroscopy, electron crystallography of negatively stained 2D crystals, and fitting of the available X-ray structure of the monomeric E1 ectodomain into the resulting 3D reconstruction. The visualized E1HT reveals that the ectodomain has reoriented vertically and inserted the distal tip of domain II into the lipid bilayer. Our data allow the visualization of a viral fusion protein inserted in its target membrane and demonstrate that insertion is a cooperative process, resulting in rings composed of five to six homotrimers.",
author = "Gibbons, {Don L.} and Inge Erk and Brigid Reilly and Jorge Navaza and Margaret Kielian and Rey, {F{\'e}lix A.} and Jean Lepault",
note = "Funding Information: We thank Y. Gaudin for comments on the manuscript and S. Bressanelli, S. Duquerroy, J. Lescar, A. Roussel, M.C. Vaney, and the members of our laboratories for help and discussions. We acknowledge support from the CNRS and INRA, the SESAME Program of the R{\'e}gion Ile-de-France, the French Fondation pour la Recherche M{\'e}dicale, the Association pour la Recherche contre le Cancer, and the CNRS programs Physique et Chimie du Vivant and Dynamique et r{\'e}activit{\'e} des assemblages biologiques. The work was also supported by a grant to M.K. from the Public Health Service (R01 GM52929) and by Cancer Center Core Support Grant NIH/NCI P30-CA13330. D.L.G. was supported through the Medical Scientist Training Program of the Albert Einstein College of Medicine (NIH T32 GM 07288) and the Albert Cass Traveling Fellowship. Data in this paper are from a thesis submitted by D.L.G. in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in the Sue Golding Graduate Division of Medical Sciences, Albert Einstein College of Medicine, Yeshiva University.",
year = "2003",
month = sep,
day = "5",
doi = "10.1016/S0092-8674(03)00683-4",
language = "English (US)",
volume = "114",
pages = "573--583",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}