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PHIST c protein family members localize to different subcellular organelles and bind Plasmodium falciparum major virulence factor Pf EMP ‐1
Author(s) -
Kumar Vikash,
Kaur Jasweer,
Singh Amrit P.,
Singh Vineeta,
Bisht Anjali,
Panda Jiban J.,
Mishra Prakash C.,
Hora Rachna
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14340
Subject(s) - plasmodium falciparum , biology , subfamily , protein subunit , protein family , microbiology and biotechnology , genetics , plasma protein binding , cytoplasm , virulence factor , virulence , gene , malaria , immunology
Plasmodium falciparum encodes a novel repertoire of the Plasmodium helical interspersed subtelomeric ( PHIST ) family of exported proteins, which play diverse roles in infected red blood cells, contributing to malaria pathogenesis. PHIST proteins are central to parasite biology and modify human erythrocytes by interacting with parasite and host proteins. Here, we have attempted to understand the localization and function of two unexplored proteins of the PHIST c subfamily, PFD 1140w and PF 11_0503, and compared these with a well‐characterized member, PFI 1780w. We demonstrate that Phist domains assume different oligomeric states owing to a distinct array of subunit interface residues. Colocalization of a Maurer's cleft signature protein, P. falciparum skeleton‐binding protein‐1 ( Pf SBP ‐1), and P. falciparum erythrocyte membrane protein‐1 ( Pf EMP ‐1) revealed different subcellular destinations for these PHIST members. We further show the binding of recombinant PHIST proteins to the cytoplasmic tail of Pf EMP ‐1 and a novel interaction with Pf SBP ‐1. Interestingly, PFD 1140w interacts with Pf EMP ‐1 and Pf SBP ‐1 simultaneously in vitro leading to formation of a complex. These two distant PHIST c members also bind Pf EMP ‐1 on distinct sites, despite sharing the Phist domain. Our data re‐emphasize a supportive role for PHIST proteins in cytoadhesion, and identify a new binding partner, Pf SBP ‐1, for members of this family. This information therefore adds another chapter to the understanding of P. falciparum biology and highlights the significance of the unexplored PHIST family.