8SXI

CH505 Disulfide Stapled SOSIP Bound to b12 Fab

Summary for 8SXI

• Entry DOI: 10.2210/pdb8sxi/pdb
• EMDB information: 40853
• Descriptor: Envelope glycoprotein gp160, HIV-1 gp41, b12 Heavy Chain, ... (4 entities in total)
• Functional Keywords: hiv-1, envelope, env, ectodomain, fusion protein, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 275880.26

Authors

Henderson, R. (deposition date: 2023-05-22, release date: 2024-02-14, Last modification date: 2024-11-13)

Primary citation

Bennett, A.L.,Edwards, R.,Kosheleva, I.,Saunders, C.,Bililign, Y.,Williams, A.,Bubphamala, P.,Manosouri, K.,Anasti, K.,Saunders, K.O.,Alam, S.M.,Haynes, B.F.,Acharya, P.,Henderson, R.
Microsecond dynamics control the HIV-1 Envelope conformation.
Sci Adv, 10:eadj0396-eadj0396, 2024

PubMed Abstract: The HIV-1 Envelope (Env) glycoprotein facilitates host cell fusion through a complex series of receptor-induced structural changes. Although remarkable progress has been made in understanding the structures of various Env conformations, microsecond timescale dynamics have not been studied experimentally. Here, we used time-resolved, temperature-jump small-angle x-ray scattering to monitor structural rearrangements in an HIV-1 Env SOSIP ectodomain construct with microsecond precision. In two distinct Env variants, we detected a transition that correlated with known Env structure rearrangements with a time constant in the hundreds of microseconds range. A previously unknown structural transition was also observed, which occurred with a time constant below 10 μs, and involved an order-to-disorder transition in the trimer apex. Using this information, we engineered an Env SOSIP construct that locks the trimer in the prefusion closed state by connecting adjacent protomers via disulfides. Our findings show that the microsecond timescale structural dynamics play an essential role in controlling the Env conformation with impacts on vaccine design.

PubMed: 38306419
DOI: 10.1126/sciadv.adj0396

Experimental method

ELECTRON MICROSCOPY (4.5 Å)