3vuu

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Crystal structure of the merozoite surface protein MSPDBL2 from P. falciparumCrystal structure of the merozoite surface protein MSPDBL2 from P. falciparum

Structural highlights

3vuu is a 1 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.093Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8IJ45_PLAF7

Publication Abstract from PubMed

Invasion of human red blood cells by Plasmodium falciparum involves interaction of the merozoite form through proteins on the surface coat. The Erythrocyte Binding-Like (EBL) protein family functions after initial merozoite interaction by binding via the Duffy Binding-Like (DBL) domain to receptors on the host red blood cell. The Merozoite Surface Proteins DBL 1 and 2 (PfMSPDBL1 and PfMSPDBL2) (PF10_0348 and PF10_0355) are extrinsically associated with the emrozite, and both have a DBL domain in each protein. We expressed and refolded recombinant DBL domains for PfMSPDBL1 and 2 and show they are functional. Binding of these domains to red blood cells is enhanced by addition of metal co-factors, which has implications for receptor binding of other DBL containing proteins in Plasmodium spp. We solved the structure of the erythrocyte-binding DBL domain of PfMSPDBL2 to 2.09 angstroms resolution and modelled that of PfMSPDBL1, revealing a canonical DBL fold consisting of a boomerang shaped alpha-helical core formed from three sub-domains. PfMSPDBL2 is highly polymorphic and mapping of these mutations shows they are on the surface, predominantly in the first two domains. For both PfMSPDBL proteins polymorphic variation spares the cleft separating domains 1 and 2 from domain 3, and the groove between the two major helices of domain 3 extending beyond the cleft, indicating these regions are functionally important and likely to be associated with the binding of a receptor on the red blood cell.

Insights into duffy binding-like domains through the crystal structure and function of the merozoite surface protein MSPDBL2 from P. falciparum.,Hodder AN, Czabotar PE, Uboldi AD, Clarke OB, Lin CS, Healer J, Smith BJ, Cowman AF J Biol Chem. 2012 Jul 26. PMID:22843685[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Hodder AN, Czabotar PE, Uboldi AD, Clarke OB, Lin CS, Healer J, Smith BJ, Cowman AF. Insights into duffy binding-like domains through the crystal structure and function of the merozoite surface protein MSPDBL2 from P. falciparum. J Biol Chem. 2012 Jul 26. PMID:22843685 doi:10.1074/jbc.M112.350504

3vuu, resolution 2.09Å

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