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Publication Abstract from PubMed

The ClpAP complex is a conserved bacterial protease that unfolds and degrades proteins targeted for destruction. The ClpA double-ring hexamer powers substrate unfolding and translocation into the ClpP proteolytic chamber. Here, we determined high-resolution structures of wild-type Escherichia coli ClpAP undergoing active substrate unfolding and proteolysis. A spiral of pore loop-substrate contacts spans both ClpA AAA+ domains. Protomers at the spiral seam undergo nucleotide-specific rearrangements, supporting substrate translocation. IGL loops extend flexibly to bind the planar, heptameric ClpP surface with the empty, symmetry-mismatched IGL pocket maintained at the seam. Three different structures identify a binding-pocket switch by the IGL loop of the lowest positioned protomer, involving release and re-engagement with the clockwise pocket. This switch is coupled to a ClpA rotation and a network of conformational changes across the seam, suggesting that ClpA can rotate around the ClpP apical surface during processive steps of translocation and proteolysis.

Conformational plasticity of the ClpAP AAA+ protease couples protein unfolding and proteolysis.,Lopez KE, Rizo AN, Tse E, Lin J, Scull NW, Thwin AC, Lucius AL, Shorter J, Southworth DR Nat Struct Mol Biol. 2020 Apr 20. pii: 10.1038/s41594-020-0409-5. doi:, 10.1038/s41594-020-0409-5. PMID:32313240^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.