8SAX

CryoEM structure of DH270.UCA-CH848.10.17DT

8SAX の概要

• エントリーDOI: 10.2210/pdb8sax/pdb
• EMDBエントリー: 40273 40274 40275 40277 40278 40279 40280 40281 40282 40283 40284 40285 40286 40287 40288 40289 40290 40291
• 分子名称: CH848.10.17.SOSIP gp120, CH848.10.17.SOSIP gp41, DH270.UCA heavy chain, ... (7 entities in total)
• 機能のキーワード: hiv-1, antibody, dh270.uca, ch848.10.17, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: HIV-1 06TG.HT008; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 288809.09

構造登録者

Henderson, R.,Zhou, Y.,Stalls, V.,Bartesaghi, B.,Acharya, P. (登録日: 2023-04-02, 公開日: 2023-04-19, 最終更新日: 2023-05-31)

主引用文献

Henderson, R.,Zhou, Y.,Stalls, V.,Wiehe, K.,Saunders, K.O.,Wagh, K.,Anasti, K.,Barr, M.,Parks, R.,Alam, S.M.,Korber, B.,Haynes, B.F.,Bartesaghi, A.,Acharya, P.
Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage.
Nat Commun, 14:2782-2782, 2023

PubMed Abstract: Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with extensive sequence diversity. Vaccine design for pathogens such as HIV-1 and influenza has therefore focused on recapitulating the natural affinity maturation process. Here, we determine structures of antibodies in complex with HIV-1 Envelope for all observed members and ancestral states of the broadly neutralizing HIV-1 V3-glycan targeting DH270 antibody clonal B cell lineage. These structures track the development of neutralization breadth from the unmutated common ancestor and define affinity maturation at high spatial resolution. By elucidating contacts mediated by key mutations at different stages of antibody development we identified sites on the epitope-paratope interface that are the focus of affinity optimization. Thus, our results identify bottlenecks on the path to natural affinity maturation and reveal solutions for these that will inform immunogen design aimed at eliciting a broadly neutralizing immune response by vaccination.

PubMed: 37188681
DOI: 10.1038/s41467-023-38108-1

実験手法

ELECTRON MICROSCOPY (4 Å)