@article{fdi:010060381,
  title = {{S}tructural and immunological correlations between the variable blocks of the {VAR}2{CSA} domain {DBL}6 epsilon from two {P}lasmodium falciparum parasite lines},
  author = {{G}angnard, {S}. and {B}adaut, {C}. and {R}amboarina, {S}. and {B}aron, {B}. and {R}amdani, {T}. and {G}amain, {B}. and {D}eloron, {P}hilippe and {L}ewit-{B}entley, {A}. and {B}entley, {G}. {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{P}lasmodium falciparum erythrocyte membrane protein 1 ({P}f{EMP}1), a family of adhesins of the falciparum species of the malaria parasite, is exposed on the surface of the infected erythrocyte. {I}n general, only one {P}f{EMP}1 variant is expressed at a time but switching between variants occurs, changing both host-cell receptor specificity and serotype. {T}he {P}f{EMP}1 variant {VAR}2{CSA} causes sequestration of infected erythrocytes in the intervillous spaces of the placenta via the glycosaminoglycan chondroitin sulfate {A}. {T}his leads to pregnancy-associated malaria, which has severe consequences for the fetus and mother. {T}he extracellular region of {VAR}2{CSA} comprises six {DBL} ({D}uffy-binding-like) domains and a single {CIDR} (cysteine-rich inter-domain region) domain. {T}he {C}-terminal domain {DBL}6 epsilon, the most polymorphic domain of {VAR}2{CSA}, has seven regions of high variability termed variable blocks ({VB}s). {H}ere we have determined the crystal structure of {DBL}6 epsilon from the {FCR}3 parasite line and have compared it with the previously determined structure of that from the 3{D}7 line. {W}e found significant differences particularly in the {N}-terminal region, which contains the first {VB} ({VB}1). {A}lthough {DBL}6 epsilon is the most variable {VAR}2{CSA} domain, {DBL}6 epsilon-{FCR}3 and {DBL}6 epsilon-3{D}7 react with {I}g{G} purified from immune sera of pregnant women. {F}urthermore, {I}g{G} purified on one domain cross-reacts with the other, confirming the presence of cross-reactive epitopes. {W}e also examined reactivity of immune sera to the four least variable {VB} ({VB}1, {VB}2, {VB}4 and {VB}5) using peptides with the consensus sequence closest, in turn, to the {FCR}3 or 3{D}7 domain. {T}hese results provide new molecular insights into immune escape by parasites expressing the {VAR}2{CSA} variant.},
  keywords = {pregnancy-associated malaria ; {P}f{EMP}1 ; crystal structure ; epitopes ; antigenicity},
  booktitle = {},
  journal = {{J}ournal of {M}olecular {B}iology},
  volume = {425},
  numero = {10},
  pages = {1697--1711},
  ISSN = {0022-2836},
  year = {2013},
  DOI = {10.1016/j.jmb.2013.02.014},
  URL = {https://www.documentation.ird.fr/hor/fdi:010060381},
}