 |
PDBsum entry 6mpv
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cell invasion
|
PDB id
|
|
|
|
6mpv
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
315 a.a.
|
|
|
|
|
|
|
|
|
|
|
276 a.a.
|
|
|
|
|
|
|
|
|
|
|
16 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of plasmodium falciparum rh5-Cyrpa-Ripr invasion complex.
|
|
|
Authors
|
|
W.Wong,
R.Huang,
S.Menant,
C.Hong,
J.J.Sandow,
R.W.Birkinshaw,
J.Healer,
A.N.Hodder,
U.Kanjee,
C.J.Tonkin,
D.Heckmann,
V.Soroka,
T.M.M.Søgaard,
T.Jørgensen,
M.T.Duraisingh,
P.E.Czabotar,
W.A.De jongh,
W.H.Tham,
A.I.Webb,
Z.Yu,
A.F.Cowman.
|
|
|
Ref.
|
|
Nature, 2019,
565,
118-121.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Plasmodium falciparum causes the severe form of malaria that has high levels of
mortality in humans. Blood-stage merozoites of P. falciparum invade
erythrocytes, and this requires interactions between multiple ligands from the
parasite and receptors in hosts. These interactions include the binding of the
Rh5-CyRPA-Ripr complex with the erythrocyte receptor basigin1,2,
which is an essential step for entry into human erythrocytes. Here we show that
the Rh5-CyRPA-Ripr complex binds the erythrocyte cell line JK-1 significantly
better than does Rh5 alone, and that this binding occurs through the insertion
of Rh5 and Ripr into host membranes as a complex with high molecular weight. We
report a cryo-electron microscopy structure of the Rh5-CyRPA-Ripr complex at
subnanometre resolution, which reveals the organization of this essential
invasion complex and the mode of interactions between members of the complex,
and shows that CyRPA is a critical mediator of complex assembly. Our structure
identifies blades 4-6 of the β-propeller of CyRPA as contact sites for Rh5 and
Ripr. The limited contacts between Rh5-CyRPA and CyRPA-Ripr are consistent with
the dissociation of Rh5 and Ripr from CyRPA for membrane insertion. A
comparision of the crystal structure of Rh5-basigin with the cryo-electron
microscopy structure of Rh5-CyRPA-Ripr suggests that Rh5 and Ripr are positioned
parallel to the erythrocyte membrane before membrane insertion. This provides
information on the function of this complex, and thereby provides insights into
invasion by P. falciparum.
|
|
|
|
|
|
|
