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.

Základní údaje

Originální název

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

Autoři

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.057

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/15:00082589

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1371/journal.pone.0119899

UT WoS

000350688100130

EID Scopus

2-s2.0-84924326545

Klíčová slova anglicky

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

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 22. 3. 2016 15:24, Mgr. Eva Špillingová

Anotace

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.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: 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 a Raymond S. NORTON. Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2. PLOS ONE. San Francisco: Public Library Science, 2015, roč. 10, č. 3, s. "nestránkováno", 18 s. ISSN 1932-6203. Dostupné z: https://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 = {https://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 a 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, roč.~10, č.~3, s.~''nestránkováno'', 18 s. ISSN~1932-6203. Dostupné z: https://doi.org/10.1371/journal.pone.0119899.

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