Crystal structure of a soluble cleaved HIV-1 envelope trimer
By J. Julien, A. Cupo, D. Sok, R. Stanfield, D. Lyumkis, M. Deller, P. Klasse, D. Burton, R. Sanders, John P. Moore and 2 more. Science, 2013
857 citations recorded by the source corpus.
Knowing the Enemy Infection of host cells by HIV-1 is mediated by an envelope glycoprotein (Env) trimeric spike on the surface of the virus. Proteins comprising the Env trimer must be cleaved for infectivity, and thus viral fusion involves three Env conformations. The flexibility of the Env trimer has made it a challenge to determine a high-resolution structure, although such a structure is key both for understanding trimer function and for guiding vaccine design. Lyumkis et al. (p. 1484) and Julien et al. (p. 1477) studied soluble cleaved trimers stabilized by specific mutations but that have kept a near-native antigenicity profile. Lyumkis et al. present a high-resolution structure of the trimer in complex with a broadly neutralizing antibody, and Julien et al. present a crystal structure of the trimer in complex with another broadly neutralizing antibody. Key structural features dictate how the HIV envelope protein functions and interacts with the human immune system. HIV-1 entry into CD4+ target cells is mediated by cleaved envelope glycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4.7 angstroms of a soluble, cleaved Env trimer that is stabilized and antigenically near-native (termed the BG505 SOSIP.664 gp140 trimer) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a prefusion state of gp41, the interaction between the component gp120 and gp41 subunits, and how a close association between the gp120 V1/V2/V3 loops stabilizes the trimer apex around the threefold axis. The complete epitope of PGT122 on the trimer involves gp120 V1, V3, and several surrounding glycans. This trimer structure advances our understanding of how Env functions and is presented to the immune system, and provides a blueprint for structure-based vaccine design.
Subfields: Molecular Biology, Radiology, Nuclear Medicine and Imaging, Virology
View Paper: https://www.semanticscholar.org/paper/c43d74e3eb72932eb7bb6229703050aabad75caa
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Citations in the corpus
- Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability (2016, positive): “This obstacle was spectacularly overcome by the BG505 SOSIP.664 gp140 trimer 11 , which facilitated high-resolution analyses of Env structure 14–16 , 35 and provided a rational In this study, we investigated the underlying causes of HIV-1 Env metastability with a rational design strategy.”
- Biological roles of glycans (2016, background): “Meanwhile, it is definitely a worthwhile exercise to model the glycans back into the crystal structure to a best approximation (501, 503).”
- Viral membrane fusion (2015, background): “Recently determined structures for a prefusion conformation HIV-1 gp120:gp41 envelope protein confirm earlier proposals that its fusogenic conformational change would follow an HA-like sequence (Bartesaghi et al., 2013; Lyumkis et al., 2013; Julien et al., 2013; Pancera et al., 2014), but the trigge”
- Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles (2016, positive): “Based on the SOSIP trimer structures 9,10,11 , we assessed particulate display of trimeric Env antigens on FR, LS and E2p nanoparticle platforms.”
- Prefusion structure of a human coronavirus spike protein (2016, background): “4) , which also have receptor-binding subunits that cap the central helix of the fusion subunit 14, 15, 27, 28 .”