Insights into the inter-ring plasticity of caseinolytic proteases from the X-ray structure of Mycobacterium tuberculosis ClpP1.
Mycobacterium tuberculosis caseinolytic protease ClpP1 (Mt ClpP1) is a self-compartmentalized protease consisting of two heptameric rings stacked on top of each other, thus enclosing a catalytic chamber. Within the chamber, which can be reached through two axial pores, each of the 14 identical monomers possesses a serine protease active site. The unfolding and translocation of substrates into the chamber are mediated by associated hexameric ATPases covering the axial pores. Three crystal structures of Mt ClpP1, determined by molecular replacement, are presented in this study. Two of the models were refined to a resolution of 2.6 A and the third to 3.0 A. It was found that disorder in the handle domain affects the formation and configuration of the tetradecamer and results in condensed structures with larger equatorial pores when compared with ClpPs from other species. Additionally, this disorder accompanies conformational changes of the residues in the catalytic triad. The models also reveal structural differences within the N-terminal hairpin-loop domain, which possibly reflect the significant differences in amino-acid sequence between Mt ClpP1 and other ClpP homologues in this region.
Ingvarsson
Henrik
H
Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden.
Maté
María J
MJ
Högbom
Martin
M
Portnoï
Denis
D
Benaroudj
Nadia
N
Alzari
Pedro M
PM
Ortiz-Lombardía
Miguel
M
Unge
Torsten
T
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D049071:Endopeptidase Clp / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D011487:Protein Conformation
D001426:Bacterial Proteins; D049071:Endopeptidase Clp