title: Structural insights into the inactive subunit of the apicoplast-localized caseinolytic protease complex of Plasmodium falciparum.
abstract: The ATP-dependent caseinolytic protease, ClpP, is highly conserved in bacteria and in the organelles of different organisms. In cyanobacteria, plant plastids, and the apicoplast of the genus Plasmodium, a noncatalytic paralog of ClpP, termed ClpR, has been identified. ClpRs are found to form heterocomplexes with ClpP resulting in a ClpRP tetradecameric cylinder having less than 14 catalytic triads. The exact role of ClpR in such a complex remains enigmatic. Here we describe the x-ray crystal structure of ClpR protein heptamer from Plasmodium falciparum (PfClpR). This is the first structure of a ClpR protein. The structure shows that the PfClpR monomer adopts a fold similar to that of ClpP, but has a unique motif, which we named the R-motif, forming a β turn located near the inactive catalytic triad in a three-dimensional space. The PfClpR heptamer exhibits a more open and flat ring than a ClpP heptamer. PfClpR was localized in the P. falciparum apicoplast as is the case of PfClpP. However, biochemical and structural data suggest that, contrary to what has been observed in other organisms, PfClpP and PfClpR do not form a stable heterocomplex in the apicoplast of P. falciparum.
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Majida
authors.initials: M
authors.lastname: El Bakkouri
authors.forename: Sumit
authors.initials: S
authors.lastname: Rathore
authors.forename: Charles
authors.initials: C
authors.lastname: Calmettes
authors.forename: Amy K
authors.initials: AK
authors.lastname: Wernimont
authors.forename: Kaiyin
authors.initials: K
authors.lastname: Liu
authors.forename: Dipto
authors.initials: D
authors.lastname: Sinha
authors.forename: Mohd
authors.initials: M
authors.lastname: Asad
authors.forename: Patrick
authors.initials: P
authors.lastname: Jung
authors.forename: Raymond
authors.initials: R
authors.lastname: Hui
authors.forename: Asif
authors.initials: A
authors.lastname: Mohmmed
authors.forename: Walid A
authors.initials: WA
authors.lastname: Houry
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002364:Caseins / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019084:Fluorescent Antibody Technique, Indirect; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015388:Organelles / Q000201:enzymology; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000201:enzymology*; D011487:Protein Conformation; D059748:Proteolysis; D017386:Sequence Homology, Amino Acid
chemical_list: D002364:Caseins; D010447:Peptide Hydrolases