2EPH

Crystal structure of fructose-bisphosphate aldolase from Plasmodium falciparum in complex with TRAP-tail determined at 2.7 angstrom resolution

Summary for 2EPH

• Entry DOI: 10.2210/pdb2eph/pdb
• Related: 1A5C 2PC4
• Descriptor: Fructose-bisphosphate aldolase, PbTRAP (3 entities in total)
• Functional Keywords: aldolase, invasion machinery, plasmodium falciparum, structural genomics, psi, protein structure initiative, structural genomics of pathogenic protozoa consortium, sgpp, lyase
• Biological source: Plasmodium falciparum (malaria parasite P. falciparum); More
• Total number of polymer chains: 5
• Total formula weight: 161403.34

Authors

Bosch, J.,Buscaglia, C.A.,Krumm, B.,Cardozo, T.,Nussenzweig, V.,Hol, W.G.J.,Structural Genomics of Pathogenic Protozoa Consortium (SGPP) (deposition date: 2007-03-30, release date: 2007-04-17, Last modification date: 2023-08-23)

Primary citation

Bosch, J.,Buscaglia, C.A.,Krumm, B.,Ingason, B.P.,Lucas, R.,Roach, C.,Cardozo, T.,Nussenzweig, V.,Hol, W.G.
Aldolase provides an unusual binding site for thrombospondin-related anonymous protein in the invasion machinery of the malaria parasite.
Proc.Natl.Acad.Sci.Usa, 104:7015-7020, 2007

PubMed Abstract: An actomyosin motor located underneath the plasma membrane drives motility and host-cell invasion of apicomplexan parasites such as Plasmodium falciparum and Plasmodium vivax, the causative agents of malaria. Aldolase connects the motor actin filaments to transmembrane adhesive proteins of the thrombospondin-related anonymous protein (TRAP) family and transduces the motor force across the parasite surface. The TRAP-aldolase interaction is a distinctive and critical trait of host hepatocyte invasion by Plasmodium sporozoites, with a likely similar interaction crucial for erythrocyte invasion by merozoites. Here, we describe 2.4-A and 2.7-A structures of P. falciparum aldolase (PfAldo) obtained from crystals grown in the presence of the C-terminal hexapeptide of TRAP from Plasmodium berghei. The indole ring of the critical penultimate Trp-residue of TRAP fits snugly into a newly formed hydrophobic pocket, which is exclusively delimited by hydrophilic residues: two arginines, one glutamate, and one glutamine. Comparison with the unliganded PfAldo structure shows that the two arginines adopt new side-chain rotamers, whereas a 25-residue subdomain, forming a helix-loop-helix unit, shifts upon binding the TRAP-tail. The structural data are in agreement with decreased TRAP binding after mutagenesis of PfAldo residues in and near the induced TRAP-binding pocket. Remarkably, the TRAP- and actin-binding sites of PfAldo seem to overlap, suggesting that both the plasticity of the aldolase active-site region and the multimeric nature of the enzyme are crucial for its intriguing nonenzymatic function in the invasion machinery of the malaria parasite.

PubMed: 17426153
DOI: 10.1073/pnas.0605301104

Experimental method

X-RAY DIFFRACTION (2.7 Å)