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

J 2015

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

MACRAILD, Christopher A., Milan ZACHRDLA, Dean ANDREW, Bankala KRISHNARJUNA, Jiří NOVÁČEK et. al.

Basic information

Original name

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

Authors

MACRAILD, Christopher A. (36 Australia), Milan ZACHRDLA (203 Czech Republic, belonging to the institution), Dean ANDREW (36 Australia), Bankala KRISHNARJUNA (36 Australia), Jiří NOVÁČEK (203 Czech Republic, belonging to the institution), Lukáš ŽÍDEK (203 Czech Republic, guarantor, belonging to the institution), Vladimír SKLENÁŘ (203 Czech Republic, belonging to the institution), Jack S. RICHARDS (36 Australia), James G. BEESON (36 Australia), Robin F. ANDERS (36 Australia) and Raymond S. NORTON (36 Australia)

Edition

PLOS ONE, San Francisco, Public Library Science, 2015, 1932-6203

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.057

RIV identification code

RIV/00216224:14740/15:00082589

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1371/journal.pone.0119899

UT WoS

000350688100130

Keywords in English

amino terminal sequence; animal experiment; animal model; antibody response; antibody specificity; antigenicity

Abstract

V originále

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 minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

Citovat

MACRAILD, Christopher A., Milan ZACHRDLA, Dean ANDREW, Bankala KRISHNARJUNA, Jiří NOVÁČEK, Lukáš ŽÍDEK, Vladimír SKLENÁŘ, Jack S. RICHARDS, James G. BEESON, Robin F. ANDERS and Raymond S. NORTON. Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2. PLOS ONE. San Francisco: Public Library Science, 2015, vol. 10, No 3, p. "nestránkováno", 18 pp. ISSN 1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0119899.

@article{1231685,
   author = {MacRaild, Christopher A. and Zachrdla, Milan and Andrew, Dean and Krishnarjuna, Bankala and Nováček, Jiří and Žídek, Lukáš and Sklenář, Vladimír and Richards, Jack S. and Beeson, James G. and Anders, Robin F. and Norton, Raymond S.},
   article_location = {San Francisco},
   article_number = {3},
   doi = {http://dx.doi.org/10.1371/journal.pone.0119899},
   keywords = {amino terminal sequence; animal experiment; animal model; antibody response; antibody specificity; antigenicity},
   language = {eng},
   issn = {1932-6203},
   journal = {PLOS ONE},
   title = {Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2},
   url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119899},
   volume = {10},
   year = {2015}
}

TY  - JOUR
ID  - 1231685
AU  - MacRaild, Christopher A. - Zachrdla, Milan - Andrew, Dean - Krishnarjuna, Bankala - Nováček, Jiří - Žídek, Lukáš - Sklenář, Vladimír - Richards, Jack S. - Beeson, James G. - Anders, Robin F. - Norton, Raymond S.
PY  - 2015
TI  - Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2
JF  - PLOS ONE
VL  - 10
IS  - 3
SP  - "nestránkováno"
EP  - "nestránkováno"
PB  - Public Library Science
SN  - 19326203
KW  - amino terminal sequence
KW  - animal experiment
KW  - animal model
KW  - antibody response
KW  - antibody specificity
KW  - antigenicity
UR  - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119899
L2  - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119899
N2  - 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 minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design.
ER  -

MACRAILD, Christopher A., Milan ZACHRDLA, Dean ANDREW, Bankala KRISHNARJUNA, Jiří NOVÁČEK, Lukáš ŽÍDEK, Vladimír SKLENÁŘ, Jack S. RICHARDS, James G. BEESON, Robin F. ANDERS and Raymond S. NORTON. Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2. \textit{PLOS ONE}. San Francisco: Public Library Science, 2015, vol.~10, No~3, p.~''nestránkováno'', 18 pp. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0119899.

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