4g4e | pdb_00004g4e

Crystal structure of the L88A mutant of HslV from Escherichia coli

spinqualitylabelsall models 4g4e, resolution 2.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4g4e is a 12 chain structure with sequence from Escherichia coli k-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: hslV (Escherichia coli K-12) Activity: HslU--HslV peptidase, with EC number 3.4.25.2 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed In all cells, ATP-dependent proteases play central roles in the controlled degradation of short-lived regulatory or misfolded proteins. A hallmark of these enzymes is that proteolytic active sites are sequestered within a compartmentalized space, which is accessible to substrates only when they are fed into the cavity by protein-unfolding ATPases. HslVU is a prototype of such enzymes, consisting of the hexameric HslU ATPase and the dodecameric HslV protease. HslV forms a barrel-shaped proteolytic chamber with two constricted axial pores. Here, we report that structural alterations of HslV's pore motif dramatically affect the proteolytic activities of both HslV and HslVU complexes. Mutations of a conserved pore residue in HslV (Leu88 to Ala, Gly, or Ser) led to a tighter binding between HslV and HslU and a dramatic stimulation of both the proteolytic and ATPase activities. Furthermore, the HslV mutants alone showed a marked increase of basal hydrolytic activities toward small peptides and unstructured proteins. A synthetic peptide of the HslU C-terminal tail further stimulated the proteolytic activities of these mutants, even allowing degradation of certain folded proteins in the absence of HslU. Moreover, expression of the L88A mutant in Escherichia coli inhibited cell growth, suggesting that HslV pore mutations dysregulate the protease through relaxing the pore constriction, which normally prevents essential cellular proteins from random degradation. Consistent with these observations, an X-ray crystal structure shows that the pore loop of L88A-HslV is largely disordered. Collectively, these results suggest that substrate degradation by HslV is controlled by gating of its pores. Structural Alteration in the Pore Motif of the Bacterial 20S Proteasome Homolog HslV Leads to Uncontrolled Protein Degradation.,Park E, Lee JW, Yoo HM, Ha BH, An JY, Jeon YJ, Seol JH, Eom SH, Chung CH J Mol Biol. 2013 May 21. pii: S0022-2836(13)00310-0. doi:, 10.1016/j.jmb.2013.05.011. PMID:23707406 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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