Conformational plasticity of the ClpAP AAA+ protease couples protein unfolding and proteolysis.
Adenosine Triphosphate
/ analogs & derivatives
Cryoelectron Microscopy
DNA Helicases
/ metabolism
Endopeptidase Clp
/ chemistry
Escherichia coli
/ chemistry
Escherichia coli Proteins
/ chemistry
Models, Molecular
Multiprotein Complexes
Protein Conformation
Protein Unfolding
Trans-Activators
/ metabolism
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
22
10
2019
accepted:
09
03
2020
pubmed:
22
4
2020
medline:
2
10
2020
entrez:
22
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32313240
doi: 10.1038/s41594-020-0409-5
pii: 10.1038/s41594-020-0409-5
pmc: PMC7529148
mid: NIHMS1625877
doi:
Substances chimiques
Escherichia coli Proteins
0
Multiprotein Complexes
0
Trans-Activators
0
replication initiator protein
0
adenosine 5'-O-(3-thiotriphosphate)
35094-46-3
Adenosine Triphosphate
8L70Q75FXE
ClpA protease, E coli
EC 3.4.21.53
ClpP protease, E coli
EC 3.4.21.92
Endopeptidase Clp
EC 3.4.21.92
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
406-416Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM099836
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM110001
Pays : United States
Organisme : NIBIB NIH HHS
ID : T32 EB009383
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008284
Pays : United States
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