7N05

Crystal structure of the F240 antibody fragment bound to the HIV-1 gp41 immunodominant region

Summary for 7N05

• Entry DOI: 10.2210/pdb7n05/pdb
• Related: 7N04
• Descriptor: Fab F240 heavy chain, Fab F240 light chain, HIV-1 gp41 immunodominant region, ... (6 entities in total)
• Functional Keywords: antibody, fab, anti-hiv, gp41, immunodominant domain, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 52876.89

Authors

Cook, J.D.,Lee, J.E. (deposition date: 2021-05-25, release date: 2022-03-30, Last modification date: 2024-10-30)

Primary citation

Cook, J.D.,Khondker, A.,Lee, J.E.
Conformational plasticity of the HIV-1 gp41 immunodominant region is recognized by multiple non-neutralizing antibodies.
Commun Biol, 5:291-291, 2022

PubMed Abstract: The early humoral immune response to acute HIV-1 infection is largely non-neutralizing. The principal target of these antibodies is the primary immunodominant region (PID) on the gp41 fusion protein. The PID is a highly conserved 15-residue region displayed on the surface of HIV-1 virions. In this study, we analyzed the humoral determinants of HIV-1 gp41 PID binding using biophysical, structural, and computational methods. In complex with a patient-derived near-germline antibody fragment, the PID motif adopts an elongated random coil, whereas the PID bound to affinity-matured Fab adopts a strand-turn-helix conformation. Molecular dynamics simulations showed that the PID is structurally plastic suggesting that the PID can form an ensemble of structural states recognized by various non-neutralizing antibodies, facilitating HIV-1 immunodominance observed in acute and chronic HIV-1 infections. An improved understanding of how the HIV-1 gp41 PID misdirects the early humoral response should guide the development of an effective HIV-1 vaccine.

PubMed: 35361878
DOI: 10.1038/s42003-022-03235-w

Experimental method

X-RAY DIFFRACTION (1.7 Å)