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Structure paper

TitleThe human ATAD5 has evolved unique structural elements to function exclusively as a PCNA unloader.
Journal, issue, pagesNat Struct Mol Biol, Year 2024
Publish dateJun 13, 2024
AuthorsFeng Wang / Qing He / Nina Y Yao / Michael E O'Donnell / Huilin Li /
PubMed AbstractHumans have three different proliferating cell nuclear antigen (PCNA) clamp-loading complexes: RFC and CTF18-RFC load PCNA onto DNA, but ATAD5-RFC can only unload PCNA from DNA. The underlying ...Humans have three different proliferating cell nuclear antigen (PCNA) clamp-loading complexes: RFC and CTF18-RFC load PCNA onto DNA, but ATAD5-RFC can only unload PCNA from DNA. The underlying structural basis of ATAD5-RFC unloading is unknown. We show here that ATAD5 has two unique locking loops that appear to tie the complex into a rigid structure, and together with a domain that plugs the DNA-binding chamber, prevent conformation changes required for DNA binding, likely explaining why ATAD5-RFC is exclusively a PCNA unloader. These features are conserved in the yeast PCNA unloader Elg1-RFC. We observe intermediates in which PCNA bound to ATAD5-RFC exists as a closed planar ring, a cracked spiral or a gapped spiral. Surprisingly, ATAD5-RFC can open a PCNA gap between PCNA protomers 2 and 3, different from the PCNA protomers 1 and 3 gap observed in all previously characterized clamp loaders.
External linksNat Struct Mol Biol / PubMed:38871854
MethodsEM (single particle)
Resolution3.04 - 4.2 Å
Structure data

42287

8ui7

EMDB-42287, PDB-8ui7:
Cryo-EM map of human clmap-clamp loader ATAD5-RFC-gapped PCNA complex in intermediate state 3
Method: EM (single particle) / Resolution: 4.2 Å

42288

8ui8

EMDB-42288, PDB-8ui8:
Cryo-EM map of human clamp-clamp loader ATAD5-RFC-two PCNAs complex in intermediate state 3
Method: EM (single particle) / Resolution: 3.1 Å

42289

8ui9

EMDB-42289, PDB-8ui9:
Cryo-EM map of human clamp-clamp loader ATAD5-RFC-cracked PCNA complex in intermediate state 2
Method: EM (single particle) / Resolution: 3.5 Å

42295

8uii

EMDB-42295, PDB-8uii:
Cryo-EM map of human clamp-clamp loader ATAD5-RFC-closed PCNA complex in intermediate state 1
Method: EM (single particle) / Resolution: 3.04 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Source
  • homo sapiens (human)
KeywordsMOTOR PROTEIN / AAA ATPase / Clamp unloader

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