6NIJ

PGT145 Fab in complex with full length AMC011 HIV-1 Env

Summary for 6NIJ

• Entry DOI: 10.2210/pdb6nij/pdb
• EMDB information: 9378
• Descriptor: PGT145 Fab heavy chain, PGT145 Fab light chain, AMC011 Glycoprotein 120, ... (7 entities in total)
• Functional Keywords: hiv-1, antibody, glycoprotein, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 307691.50

Authors

Cottrell, C.A.,Torrents de la Pena, A.,Rantalainen, K.,Torres, J.L.,Ward, A.B. (deposition date: 2018-12-29, release date: 2019-07-31, Last modification date: 2023-04-05)

Primary citation

Torrents de la Pena, A.,Rantalainen, K.,Cottrell, C.A.,Allen, J.D.,van Gils, M.J.,Torres, J.L.,Crispin, M.,Sanders, R.W.,Ward, A.B.
Similarities and differences between native HIV-1 envelope glycoprotein trimers and stabilized soluble trimer mimetics.
Plos Pathog., 15:e1007920-e1007920, 2019

PubMed Abstract: The HIV-1 envelope glycoprotein (Env) trimer is located on the surface of the virus and is the target of broadly neutralizing antibodies (bNAbs). Recombinant native-like soluble Env trimer mimetics, such as SOSIP trimers, have taken a central role in HIV-1 vaccine research aimed at inducing bNAbs. We therefore performed a direct and thorough comparison of a full-length unmodified Env trimer containing the transmembrane domain and the cytoplasmic tail, with the sequence matched soluble SOSIP trimer, both based on an early Env sequence (AMC011) from an HIV+ individual that developed bNAbs. The structures of the full-length AMC011 trimer bound to either bNAb PGT145 or PGT151 were very similar to the structures of SOSIP trimers. Antigenically, the full-length and SOSIP trimers were comparable, but in contrast to the full-length trimer, the SOSIP trimer did not bind at all to non-neutralizing antibodies, most likely as a consequence of the intrinsic stabilization of the SOSIP trimer. Furthermore, the glycan composition of full-length and SOSIP trimers was similar overall, but the SOSIP trimer possessed slightly less complex and less extensively processed glycans, which may relate to the intrinsic stabilization as well as the absence of the membrane tether. These data provide insights into how to best use and improve membrane-associated full-length and soluble SOSIP HIV-1 Env trimers as immunogens.

PubMed: 31306470
DOI: 10.1371/journal.ppat.1007920

Experimental method

ELECTRON MICROSCOPY (5.7 Å)