PDBsum entry 4jle

Protein binding

PDB id: 4jle

Contents

Protein chains

149 a.a.

159 a.a.

Ligands

ACT

Metals

_CL ×6

Waters ×47

PDB id:

4jle

Name:

Protein binding

Title:

Structure of the p. Falciparum pfi1780w phist domain

Structure:

Phist. Chain: a, b. Engineered: yes

Source:

Plasmodium falciparum. Organism_taxid: 36329. Strain: p. Falciparum 3d7. Gene: pfi1780w. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.35Å R-factor: 0.209 R-free: 0.255

Authors:

L.Slater,I.Vakonakis

Key ref:

A.Oberli et al. (2014). A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface. Faseb J, 28, 4420-4433. PubMed id: 24983468 DOI: 10.1096/fj.14-256057

Date:

12-Mar-13 Release date: 16-Apr-14

Protein chain

Q8I2F2  (Q8I2F2_PLAF7) -  Plasmodium RESA N-terminal domain-containing protein from Plasmodium falciparum (isolate 3D7)

Seq: 383 a.a.

Struc: 149 a.a.

Protein chain

Q8I2F2  (Q8I2F2_PLAF7) -  Plasmodium RESA N-terminal domain-containing protein from Plasmodium falciparum (isolate 3D7)

Seq: 383 a.a.

Struc: 159 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1096/fj.14-256057

Faseb J 28:4420-4433 (2014)

PubMed id: 24983468

A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface.

A.Oberli, L.M.Slater, E.Cutts, F.Brand, E.Mundwiler-Pachlatko, S.Rusch, M.F.Masik, M.C.Erat, H.P.Beck, I.Vakonakis.

ABSTRACT

Uniquely among malaria parasites, Plasmodium falciparum-infected erythrocytes (iRBCs) develop membrane protrusions, known as knobs, where the parasite adhesion receptor P. falciparum erythrocyte membrane protein 1 (PfEMP1) clusters. Knob formation and the associated iRBC adherence to host endothelium are directly linked to the severity of malaria and are functional manifestations of protein export from the parasite to the iRBC. A family of exported proteins featuring Plasmodium helical interspersed subtelomeric (PHIST) domains has attracted attention, with members being implicated in host-parasite protein interactions and differentially regulated in severe disease and among parasite isolates. Here, we show that PHIST member PFE1605w binds the PfEMP1 intracellular segment directly with Kd = 5 ± 0.6 μM, comigrates with PfEMP1 during export, and locates in knobs. PHIST variants that do not locate in knobs (MAL8P1.4) or bind PfEMP1 30 times more weakly (PFI1780w) used as controls did not display the same pattern. We resolved the first crystallographic structure of a PHIST protein and derived a partial model of the PHIST-PfEMP1 interaction from nuclear magnetic resonance. We propose that PFE1605w reinforces the PfEMP1-cytoskeletal connection in knobs and discuss the possible role of PHIST proteins as interaction hubs in the parasite exportome.