6RCU

PfRH5 bound to monoclonal antibodies R5.004 and R5.016

6RCU の概要

• エントリーDOI: 10.2210/pdb6rcu/pdb
• 関連するPDBエントリー: 6RCO 6RCQ 6RCS
• 分子名称: Reticulocyte binding protein homologue 5, R5.004 heavy chain, R5.004 light chain, ... (5 entities in total)
• 機能のキーワード: plasmodium falciparum erythrocyte invasion potentiating antibody neutralising antibody human monoclonal antibody, cell adhesion
• 由来する生物種: Plasmodium falciparum (isolate 3D7); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 182555.43

構造登録者

Alanine, D.W.G.,Draper, S.J.,Higgins, M.K. (登録日: 2019-04-11, 公開日: 2019-06-26, 最終更新日: 2024-11-06)

主引用文献

Alanine, D.G.W.,Quinkert, D.,Kumarasingha, R.,Mehmood, S.,Donnellan, F.R.,Minkah, N.K.,Dadonaite, B.,Diouf, A.,Galaway, F.,Silk, S.E.,Jamwal, A.,Marshall, J.M.,Miura, K.,Foquet, L.,Elias, S.C.,Labbe, G.M.,Douglas, A.D.,Jin, J.,Payne, R.O.,Illingworth, J.J.,Pattinson, D.J.,Pulido, D.,Williams, B.G.,de Jongh, W.A.,Wright, G.J.,Kappe, S.H.I.,Robinson, C.V.,Long, C.A.,Crabb, B.S.,Gilson, P.R.,Higgins, M.K.,Draper, S.J.
Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.
Cell, 178:216-228.e21, 2019

PubMed Abstract: The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria.

PubMed: 31204103
DOI: 10.1016/j.cell.2019.05.025

実験手法

X-RAY DIFFRACTION (4.005 Å)