title: Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer.
abstract: The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric glycoprotein precursor, gp160, into three gp120 and three gp41 subunits. Here, we describe an ~11-Å cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain and a trimer-association domain of gp120 composed of the V1, V2 and V3 variable regions. The cage-like architecture, which is unique among characterized viral envelope proteins, restricts antibody access, reflecting requirements imposed by HIV-1 persistence in the host.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Youdong
authors.initials: Y
authors.lastname: Mao
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Christopher
authors.initials: C
authors.lastname: Gu
authors.forename: Alon
authors.initials: A
authors.lastname: Herschhorn
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Xiang
authors.forename: Hillel
authors.initials: H
authors.lastname: Haim
authors.forename: Xinzhen
authors.initials: X
authors.lastname: Yang
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D002460:Cell Line; D020285:Cryoelectron Microscopy; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
chemical_list: D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D021122:Protein Subunits