The Human ATAD5 Has Evolved Unique Structural Elements to Function Exclusively As a PCNA Unloader

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2024 Jun 13

PMID 38871854

Authors

Feng Wang

Qing He

Nina Y Yao

Michael E ODonnell

Huilin Li

Affiliations

Soon will be listed here.

Abstract

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.

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