Structural highlights
Function
[HSLU_HAEIN] ATPase subunit of a proteasome-like degradation complex; this subunit has chaperone activity. The binding of ATP and its subsequent hydrolysis by HslU are essential for unfolding of protein substrates subsequently hydrolyzed by HslV. HslU recognizes the N-terminal part of its protein substrates and unfolds these before they are guided to HslV for hydrolysis. [HSLV_HAEIN] Protease subunit of a proteasome-like degradation complex believed to be a general protein degrading machinery.[HAMAP-Rule:MF_00248]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
On the basis of the structure of a HslUV complex, a mechanism of allosteric activation of the HslV protease, wherein binding of the HslU chaperone propagates a conformational change to the active site cleft of the protease, has been proposed. Here, the 3.1 A X-ray crystallographic structure of Haemophilus influenzae HslUV complexed with a vinyl sulfone inhibitor is described. The inhibitor, which reacts to form a covalent linkage to Thr1 of HslV, binds in an "antiparallel beta" manner, with hydrogen-bond interactions between the peptide backbone of the protease and that of the inhibitor, and with two leucinyl side chains of the inhibitor binding in the S1 and S3 specificity pockets of the protease. Comparison of the structure of the HslUV-inhibitor complex with that of HslV without inhibitor and in the absence of HslU reveals that backbone interactions would correctly position a substrate for cleavage in the HslUV complex, but not in the HslV protease alone, corroborating the proposed mechanism of allosteric activation. This activation mechanism differs from that of the eukaryotic proteasome, for which binding of activators opens a gated channel that controls access of substrates to the protease, but does not perturb the active site environment.
Crystal structure of HslUV complexed with a vinyl sulfone inhibitor: corroboration of a proposed mechanism of allosteric activation of HslV by HslU.,Sousa MC, Kessler BM, Overkleeft HS, McKay DB J Mol Biol. 2002 May 3;318(3):779-85. PMID:12054822[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sousa MC, Kessler BM, Overkleeft HS, McKay DB. Crystal structure of HslUV complexed with a vinyl sulfone inhibitor: corroboration of a proposed mechanism of allosteric activation of HslV by HslU. J Mol Biol. 2002 May 3;318(3):779-85. PMID:12054822 doi:10.1016/S0022-2836(02)00145-6
