The Structure of the Cysteine-Rich Domain of Plasmodium falciparum P113 Identifies the Location of the RH5 Binding Site

Author:

Campeotto Ivan12ORCID,Galaway Francis3,Mehmood Shahid4,Barfod Lea K.5ORCID,Quinkert Doris5,Kotraiah Vinayaka6,Phares Timothy W.6,Wright Katherine E.1,Snijders Ambrosius P.4,Draper Simon J.5ORCID,Higgins Matthew K.1ORCID,Wright Gavin J.3ORCID

Affiliation:

1. Department of Biochemistry, University of Oxford, Oxford, United Kingdom

2. Department of Biochemistry, Nottingham Trent University, Nottingham, United Kingdom

3. Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, United Kingdom

4. Protein Analysis and Proteomics Platform, The Francis Crick Institute, London, United Kingdom

5. The Jenner Institute, University of Oxford, Oxford, United Kingdom

6. Leidos Life Sciences, Leidos Inc., Frederick, Maryland, USA

Abstract

Malaria is a deadly infectious disease primarily caused by the parasite Plasmodium falciparum . It remains a major global health problem, and there is no highly effective vaccine. A parasite protein called RH5 is centrally involved in the invasion of host red blood cells, making it—and the other parasite proteins it interacts with—promising vaccine targets. We recently identified a protein called P113 that binds RH5, suggesting that it anchors RH5 to the parasite surface. In this paper, we use structural biology to locate and characterize the RH5 binding region on P113. These findings will be important to guide the development of new antimalarial vaccines to ultimately prevent this disease, which affects some of the poorest people on the planet.

Funder

Wellcome Trust

Francis Crick Institute

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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