Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2

PloS One
Christopher A MacRaildRaymond S Norton

Abstract

Merozoite surface protein 2 (MSP2) of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27) using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- and C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minim...Continue Reading

References

Dec 10, 1990·FEBS Letters·A S Kolaskar, P C Tongaonkar
Mar 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J A SmytheR F Anders
Dec 1, 1990·Molecular and Biochemical Parasitology·A W ThomasJ A Lyon
Mar 1, 1990·Molecular and Biochemical Parasitology·J A SmytheR F Anders
Jan 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J NovotnýG D Rose
Jan 1, 1987·Annual Review of Microbiology·D J KempR F Anders
Sep 1, 1995·Journal of Biomolecular NMR·N A FarrowL E Kay
Dec 2, 2000·Journal of Biomolecular NMR·D Sharma, K Rajarathnam
May 23, 2002·Biochemistry·A Keith DunkerZoran Obradović
Apr 26, 2003·Journal of Magnetic Resonance·Philippe PelupessyGeoffrey Bodenhausen
Aug 12, 2004·Chemical Reviews·Arthur G Palmer
Oct 27, 2004·Infection and Immunity·Christian FlückIngrid Felger
Aug 12, 2005·Journal of Molecular Recognition : JMR·Vladimir N UverskyA Keith Dunker
Apr 26, 2006·Immunome Research·Jens Erik Pontoppidan LarsenMorten Nielsen
May 2, 2006·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Christian FlückIngrid Felger
Oct 3, 2006·Molecular and Biochemical Parasitology·Zhi-Ping FengRaymond S Norton
Apr 14, 2007·The Journal of Chemical Physics·Philippe PelupessyGeoffrey Bodenhausen
May 20, 2009·Molecular and Biochemical Parasitology·Christopher G AddaRobin F Anders
Oct 23, 2009·Trends in Biochemical Sciences·Anthony K Mittermaier, Lewis E Kay
Jan 12, 2010·Human Vaccines·Robin F AndersRaymond S Norton
Apr 30, 2010·Molecular Biology and Evolution·Martine M ZilversmitDaniel L Hartl

❮ Previous
Next ❯

Citations

Dec 30, 2015·Structure·Christopher A MacRaildRaymond S Norton
Aug 29, 2020·Proceedings of the National Academy of Sciences of the United States of America·Deborah L BurnettDaniel Christ
Oct 3, 2018·Communications Biology·Bankala KrishnarjunaChristopher A MacRaild
Jan 29, 2020·Proceedings of the National Academy of Sciences of the United States of America·Mark D LangowskiSheetij Dutta
May 1, 2018·Peptide Science·Christopher A MacRaildRaymond S Norton
Jul 28, 2019·Scientific Reports·Karen S HarrisMarilyn A Anderson
Nov 26, 2020·International Journal of Molecular Sciences·Julio Angel Vázquez-MartínezVianney Ortiz-Navarrete

❮ Previous
Next ❯

Datasets Mentioned

BETA
JN248383

Methods Mentioned

BETA
affinity purification
NMR
ELISA

Software Mentioned

Bepipred

Related Concepts

Related Feeds

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.