8QKS

Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) bound to R5.034

8QKS の概要

• エントリーDOI: 10.2210/pdb8qks/pdb
• 分子名称: Reticulocyte-binding protein-like protein 5, Immunoglobulin lambda variable 1-36, R5034HV (3 entities in total)
• 機能のキーワード: malaria rh5 antibody clonotype, immune system
• 由来する生物種: Plasmodium falciparum (malaria parasite P. falciparum); 詳細
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 495233.11

構造登録者

Wright, N.D.,Barrett, J.R.,Bradshaw, W.J.,Paterson, N.G.,MacLean, E.M.,Ferreira, L.,McHugh, K.,Von Delft, F.,Koekemoer, L.,Draper, S.J. (登録日: 2023-09-16, 公開日: 2024-07-31, 最終更新日: 2024-09-18)

主引用文献

Barrett, J.R.,Pipini, D.,Wright, N.D.,Cooper, A.J.R.,Gorini, G.,Quinkert, D.,Lias, A.M.,Davies, H.,Rigby, C.A.,Aleshnick, M.,Williams, B.G.,Bradshaw, W.J.,Paterson, N.G.,Martinson, T.,Kirtley, P.,Picard, L.,Wiggins, C.D.,Donnellan, F.R.,King, L.D.W.,Wang, L.T.,Popplewell, J.F.,Silk, S.E.,de Ruiter Swain, J.,Skinner, K.,Kotraiah, V.,Noe, A.R.,MacGill, R.S.,King, C.R.,Birkett, A.J.,Soisson, L.A.,Minassian, A.M.,Lauffenburger, D.A.,Miura, K.,Long, C.A.,Wilder, B.K.,Koekemoer, L.,Tan, J.,Nielsen, C.M.,McHugh, K.,Draper, S.J.
Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype.
Cell, 187:4964-, 2024

PubMed Abstract: The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria.

PubMed: 39059380
DOI: 10.1016/j.cell.2024.06.015

実験手法

X-RAY DIFFRACTION (3.994 Å)