Cryo-EM structures reveal high-resolution mechanism of a DNA polymerase sliding clamp loader

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F22%3A00127475" target="_blank" >RIV/00216224:14740/22:00127475 - isvavai.cz</a>

Result on the web

<a href="https://elifesciences.org/articles/74175" target="_blank" >https://elifesciences.org/articles/74175</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.7554/eLife.74175" target="_blank" >10.7554/eLife.74175</a>

Result language

angličtina

Original language name

Cryo-EM structures reveal high-resolution mechanism of a DNA polymerase sliding clamp loader

Original language description

Sliding clamps are ring-shaped protein complexes that are integral to the DNA replication machinery of all life. Sliding clamps are opened and installed onto DNA by clamp loader AAA+ ATPase complexes. However, how a clamp loader opens and closes the sliding clamp around DNA is still unknown. Here, we describe structures of the Saccharomyces cerevisiae clamp loader Replication Factor C (RFC) bound to its cognate sliding clamp Proliferating Cell Nuclear Antigen (PCNA) en route to successful loading. RFC first binds to PCNA in a dynamic, closed conformation that blocks both ATPase activity and DNA binding. RFC then opens the PCNA ring through a large-scale ‘crab-claw’ expansion of both RFC and PCNA that explains how RFC prefers initial binding of PCNA over DNA. Next, the open RFC:PCNA complex binds DNA and interrogates the primer-template junction using a surprising base-flipping mechanism. Our structures indicate that initial PCNA opening and subsequent closure around DNA do not require ATP hydrolysis, but are driven by binding energy. ATP hydrolysis, which is necessary for RFC release, is triggered by interactions with both PCNA and DNA, explaining RFC’s switch-like ATPase activity. Our work reveals how a AAA+ machine undergoes dramatic conformational changes for achieving binding preference and substrate remodeling.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LL2008" target="_blank" >LL2008: Crosstalk between transcription and translation</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

elife

ISSN

2050-084X

e-ISSN

—

Volume of the periodical

11

Issue of the periodical within the volume

FEB

Country of publishing house

GB - UNITED KINGDOM

Number of pages

29

Pages from-to

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UT code for WoS article

000766980900001

EID of the result in the Scopus database

2-s2.0-85125582512