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A repeat sequence domain of the ring‐exported protein‐1 of P lasmodium falciparum controls export machinery architecture and virulence protein trafficking
Author(s) -
McHugh Emma,
Batinovic Steven,
Hanssen Eric,
McMillan Paul J.,
Kenny Shan,
Griffin Michael D. W.,
Crawford Simon,
Trenholme Katharine R.,
Gardiner Donald L.,
Dixon Matthew W. A.,
Tilley Leann
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13201
Subject(s) - biology , red blood cell , virulence , transport protein , plasmodium falciparum , membrane protein , microbiology and biotechnology , cell membrane , cell , membrane , gene , genetics , biochemistry , immunology , malaria
Summary The malaria parasite P lasmodium falciparum dramatically remodels its host red blood cell to enhance its own survival, using a secretory membrane system that it establishes outside its own cell. Cisternal organelles, called Maurer's clefts, act as a staging point for the forward trafficking of virulence proteins to the red blood cell ( RBC ) membrane. The R ing‐ EX ported P rotein‐1 ( REX 1) is a M aurer's cleft resident protein. We show that inducible knockdown of REX 1 causes stacking of M aurer's cleft cisternae without disrupting the organization of the knob‐associated histidine‐rich protein at the RBC membrane. Genetic dissection of the REX 1 sequence shows that loss of a repeat sequence domain results in the formation of giant M aurer's cleft stacks. The stacked M aurer's clefts are decorated with tether‐like structures and retain the ability to dock onto the RBC membrane skeleton. The REX 1 mutant parasites show deficient export of the major virulence protein, PfEMP 1, to the red blood cell surface and markedly reduced binding to the endothelial cell receptor, CD 36. REX 1 is predicted to form a largely α‐helical structure, with a repetitive charge pattern in the repeat sequence domain, providing potential insights into the role of REX 1 in M aurer's cleft sculpting.