7TI6

Crystal structure of the wild-type least mutated common ancestor (LMCA) of the HIV-targeting PCT64 antibody lineage

7TI6 の概要

• エントリーDOI: 10.2210/pdb7ti6/pdb
• 分子名称: PCT64_LMCA Fab heavy chain, PCT64_LMCA light chain (wild type), 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total)
• 機能のキーワード: antibody, broadly neutralizing, hiv-1, v2 apex, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49346.84

構造登録者

Omorodion, O.,Wilson, I.A. (登録日: 2022-01-12, 公開日: 2022-10-05, 最終更新日: 2024-10-23)

主引用文献

Willis, J.R.,Berndsen, Z.T.,Ma, K.M.,Steichen, J.M.,Schiffner, T.,Landais, E.,Liguori, A.,Kalyuzhniy, O.,Allen, J.D.,Baboo, S.,Omorodion, O.,Diedrich, J.K.,Hu, X.,Georgeson, E.,Phelps, N.,Eskandarzadeh, S.,Groschel, B.,Kubitz, M.,Adachi, Y.,Mullin, T.M.,Alavi, N.B.,Falcone, S.,Himansu, S.,Carfi, A.,Wilson, I.A.,Yates 3rd, J.R.,Paulson, J.C.,Crispin, M.,Ward, A.B.,Schief, W.R.
Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors.
Immunity, 55:2149-2167.e9, 2022

PubMed Abstract: Broadly neutralizing antibodies (bnAbs) to the HIV envelope (Env) V2-apex region are important leads for HIV vaccine design. Most V2-apex bnAbs engage Env with an uncommonly long heavy-chain complementarity-determining region 3 (HCDR3), suggesting that the rarity of bnAb precursors poses a challenge for vaccine priming. We created precursor sequence definitions for V2-apex HCDR3-dependent bnAbs and searched for related precursors in human antibody heavy-chain ultradeep sequencing data from 14 HIV-unexposed donors. We found potential precursors in a majority of donors for only two long-HCDR3 V2-apex bnAbs, PCT64 and PG9, identifying these bnAbs as priority vaccine targets. We then engineered ApexGT Env trimers that bound inferred germlines for PCT64 and PG9 and had higher affinities for bnAbs, determined cryo-EM structures of ApexGT trimers complexed with inferred-germline and bnAb forms of PCT64 and PG9, and developed an mRNA-encoded cell-surface ApexGT trimer. These methods and immunogens have promise to assist HIV vaccine development.

PubMed: 36179689
DOI: 10.1016/j.immuni.2022.09.001

実験手法

X-RAY DIFFRACTION (2.64 Å)