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PDBsum entry 4xbi
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References listed in PDB file
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Key reference
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Title
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Structural mapping of the clpb atpases of plasmodium falciparum: targeting protein folding and secretion for antimalarial drug design.
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Authors
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A.P.Ahyoung,
A.Koehl,
D.Cascio,
P.F.Egea.
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Ref.
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Protein Sci, 2015,
24,
1508-1520.
[DOI no: ]
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PubMed id
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Abstract
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Caseinolytic chaperones and proteases (Clp) belong to the AAA+ protein
superfamily and are part of the protein quality control machinery in cells. The
eukaryotic parasite Plasmodium falciparum, the causative agent of malaria, has
evolved an elaborate network of Clp proteins including two distinct ClpB
ATPases. ClpB1 and ClpB2 are involved in different aspects of parasitic
proteostasis. ClpB1 is present in the apicoplast, a parasite-specific and
plastid-like organelle hosting various metabolic pathways necessary for parasite
growth. ClpB2 localizes to the parasitophorous vacuole membrane where it drives
protein export as core subunit of a parasite-derived protein secretion complex,
the Plasmodium Translocon of Exported proteins (PTEX); this process is central
to parasite virulence and survival in the human host. The functional
associations of these two chaperones with parasite-specific metabolism and
protein secretion make them prime drug targets. ClpB proteins function as
unfoldases and disaggregases and share a common architecture consisting of four
domains-a variable N-terminal domain that binds different protein substrates,
followed by two highly conserved catalytic ATPase domains, and a C-terminal
domain. Here, we report and compare the first crystal structures of the N
terminal domains of ClpB1 and ClpB2 from Plasmodium and analyze their molecular
surfaces. Solution scattering analysis of the N domain of ClpB2 shows that the
average solution conformation is similar to the crystalline structure. These
structures represent the first step towards the characterization of these two
malarial chaperones and the reconstitution of the entire PTEX to aid
structure-based design of novel anti-malarial drugs.
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