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7EKB

Crystal structure of 4E10 modified with pyrene acetamide

Summary for 7EKB
Entry DOI10.2210/pdb7ekb/pdb
DescriptorFab region of the heavy chain of broadly neutralizing antibody anti-HIV-1 4E10, Fab region of the light chain of the broadly neutralizing anti-HIV-1 antibody 4E10, MPER region of the HIV-1 envelope glycoprotein protein gp41, ... (6 entities in total)
Functional Keywordsigg, fab, chemical modification, immune system
Biological sourceHomo sapiens
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Total number of polymer chains3
Total formula weight49998.86
Authors
Caaveiro, J.M.M.,Rujas, E.,Nieva, J.L. (deposition date: 2021-04-05, release date: 2021-08-11, Last modification date: 2024-11-20)
Primary citationRujas, E.,Leaman, D.P.,Insausti, S.,Carravilla, P.,Garcia-Porras, M.,Largo, E.,Morillo, I.,Sanchez-Eugenia, R.,Zhang, L.,Cui, H.,Iloro, I.,Elortza, F.,Julien, J.P.,Eggeling, C.,Zwick, M.B.,Caaveiro, J.M.M.,Nieva, J.L.
Focal accumulation of aromaticity at the CDRH3 loop mitigates 4E10 polyreactivity without altering its HIV neutralization profile.
Iscience, 24:102987-102987, 2021
Cited by
PubMed Abstract: Broadly neutralizing antibodies (bnAbs) against HIV-1 are frequently associated with the presence of autoreactivity/polyreactivity, a property that can limit their use as therapeutic agents. The bnAb 4E10, targeting the conserved Membrane proximal external region (MPER) of HIV-1, displays almost pan-neutralizing activity across globally circulating HIV-1 strains but exhibits nonspecific off-target interactions with lipid membranes. The hydrophobic apex of the third complementarity-determining region of the heavy chain (CDRH3) loop, which is essential for viral neutralization, critically contributes to this detrimental effect. Here, we have replaced the aromatic/hydrophobic residues from the apex of the CDRH3 of 4E10 with a single aromatic molecule through chemical modification to generate a variant that preserves the neutralization potency and breadth of 4E10 but with reduced autoreactivity. Collectively, our study suggests that the localized accumulation of aromaticity by chemical modification provides a pathway to ameliorate the adverse effects triggered by the CDRH3 of anti-HIV-1 MPER bnAbs.
PubMed: 34505005
DOI: 10.1016/j.isci.2021.102987
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.45 Å)
Structure validation

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数据于2025-07-30公开中

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