Structural and functional insight into how the Plasmodium falciparum VAR2CSA protein mediates binding to chondroitin sulfate A in placental malaria.

The Journal of Biological Chemistry
Thomas M ClausenAli Salanti

Abstract

Malaria is a major global health problem. Pregnant women are susceptible to infection regardless of previously acquired immunity. Placental malaria is caused by parasites capable of sequestering in the placenta. This is mediated by VAR2CSA, a parasite antigen that interacts with chondroitin sulfate A (CSA). One vaccine strategy is to block this interaction with VAR2CSA-specific antibodies. It is a priority to define a small VAR2CSA fragment that can be used in an adhesion blocking vaccine. In this, the obvious approach is to define regions of VAR2CSA involved in receptor binding. It has been shown that full-length recombinant VAR2CSA binds specifically to CSA with nanomolar affinity, and that the CSA-binding site lies in the N-terminal part of the protein. In this study we define the minimal binding region by truncating VAR2CSA and analyzing CSA binding using biosensor technology. We show that the core CSA-binding site lies within the DBL2X domain and parts of the flanking interdomain regions. This is in contrast to the idea that single domains do not possess the structural requirements for specific CSA binding. Small-angle x-ray scattering measurements enabled modeling of VAR2CSA and showed that the CSA-binding DBL2X domain is...Continue Reading

References

Nov 4, 1976·Journal of Molecular Biology·M T RecordP De Haseth
Jan 1, 1989·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·A D Cardin, H J Weintraub
Jun 19, 1998·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·R E HilemanR J Linhardt
May 1, 1999·Journal of Structural Biology·W WriggersJ A McCammon
Nov 9, 2000·Molecular and Biochemical Parasitology·J D SmithL H Miller
Nov 3, 2004·The Journal of Experimental Medicine·Ali SalantiThor G Theander
Aug 3, 2007·Molecular and Biochemical Parasitology·Joseph BockhorstJoseph D Smith
Feb 20, 2008·PLoS Pathogens·Pernille AndersenAli Salanti
Jun 14, 2008·The Journal of Biological Chemistry·Matthew K Higgins
Aug 15, 2008·The Journal of Infectious Diseases·Pamela MagistradoMorten A Nielsen
Jan 13, 2009·Clinical Microbiology Reviews·Denise L DoolanJ Kevin Baird
Jan 28, 2009·Nature Structural & Molecular Biology·Kavita SinghDavid N Garboczi
Mar 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Anand SrivastavaBenoît Gamain
Mar 15, 2011·The Journal of Biological Chemistry·Madeleine DahlbäckAli Salanti
Jun 1, 2011·PloS One·Anand SrivastavaBenoît Gamain
Apr 1, 2009·Journal of Applied Crystallography·Daniel Franke, Dmitri I Svergun

❮ Previous
Next ❯

Citations

Mar 2, 2013·The Journal of Infectious Diseases·Alfredo MayorChetan E Chitnis
Aug 13, 2013·PloS One·Eduard Rovira-VallbonaAlfredo Mayor
Feb 12, 2014·PloS One·Manuel E PatarroyoManuel A Patarroyo
Apr 25, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paulina AmpomahLars Hviid
Jun 9, 2015·Expert Opinion on Biological Therapy·Nicaise Tuikue-Ndam, Phillipe Deloron
Oct 16, 2015·Vaccine·Michal Fried, Patrick E Duffy
Jan 7, 2016·Frontiers in Microbiology·Chloe R McDonaldKevin C Kain
Oct 16, 2015·Cancer Cell·Ali SalantiMads Daugaard
Apr 5, 2013·Biological Reviews of the Cambridge Philosophical Society·Eyal KamhiRobert J Linhardt
Jan 21, 2014·Protein Science : a Publication of the Protein Society·Matthew K Higgins, Mark Carrington
Aug 21, 2013·Cellular Microbiology·Joseph D SmithThomas Lavstsen
Jul 15, 2015·Current Opinion in Immunology·Alberto Moreno, Chester Joyner
Apr 22, 2015·Emerging Infectious Diseases·Nicaise Tuikue NdamPhilippe Deloron
Apr 29, 2014·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Bita BordbarAudrey Sabbagh
May 18, 2016·The Journal of Infectious Diseases·Justin Yai Alamou DoritchamouPatrick E Duffy
Oct 31, 2016·Trends in Parasitology·Andrew TeoStephen J Rogerson
Apr 25, 2017·Expert Review of Vaccines·Caroline PehrsonMorten A Nielsen
Apr 29, 2015·The American Journal of Tropical Medicine and Hygiene·Mark A TravassosChristopher V Plowe
Dec 30, 2015·The American Journal of Tropical Medicine and Hygiene·Anna BabakhanyanDiane Wallace Taylor
Jun 13, 2017·Nature Reviews. Microbiology·Mats WahlgrenReetesh R Akhouri
Feb 28, 2018·Biotechnology and Bioengineering·Zhengxiong ZhouZhen Kang
Jul 20, 2017·The Korean Journal of Parasitology·Seon-Hee KimHyun-Jong Yang
Jan 25, 2018·Malaria Journal·Robert VeritySteven R Meshnick

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.