Structural characterisation of the complete cycle of sliding clamp loading in Escherichia coli

Ring-shaped DNA sliding clamps are essential for DNA replication and genome maintenance. Clamps need to be opened and chaperoned onto DNA by clamp loader complexes (CLCs). Detailed understanding of the mechanisms by which CLCs open and place clamps around DNA remains incomplete. Here, we present a s...

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Bibliographic Details
Published in:	Nature communications Vol. 15; no. 1; pp. 8372 - 14
Main Authors:	Xu, Zhi-Qiang, Jergic, Slobodan, Lo, Allen T. Y., Pradhan, Alok C., Brown, Simon H. J., Bouwer, James C., Ghodke, Harshad, Lewis, Peter J., Tolun, Gökhan, Oakley, Aaron J., Dixon, Nicholas E.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 27-09-2024 Nature Publishing Group Nature Portfolio
Subjects:	101/28 631/45/147 631/45/607/1159 631/535/1258/1259 82/103 Adenosine Triphosphate - metabolism Binding Clamps Cryoelectron Microscopy Deoxyribonucleic acid DNA DNA biosynthesis DNA Polymerase III - chemistry DNA Polymerase III - metabolism DNA repair DNA Replication DNA, Bacterial - genetics DNA, Bacterial - metabolism E coli Escherichia coli Escherichia coli - genetics Escherichia coli - metabolism Escherichia coli Proteins - chemistry Escherichia coli Proteins - genetics Escherichia coli Proteins - metabolism Humanities and Social Sciences Intermediates Models, Molecular Molecular machines multidisciplinary Replication Science Science (multidisciplinary) Sliding Structural analysis
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Summary:	Ring-shaped DNA sliding clamps are essential for DNA replication and genome maintenance. Clamps need to be opened and chaperoned onto DNA by clamp loader complexes (CLCs). Detailed understanding of the mechanisms by which CLCs open and place clamps around DNA remains incomplete. Here, we present a series of six structures of the Escherichia coli CLC bound to an open or closed clamp prior to and after binding to a primer-template DNA, representing the most significant intermediates in the clamp loading process. We show that the ATP-bound CLC first binds to a clamp, then constricts to hold onto it. The CLC then expands to open the clamp with a gap large enough for double-stranded DNA to enter. Upon binding to DNA, the CLC constricts slightly, allowing clamp closing around DNA. These structures provide critical high-resolution snapshots of clamp loading by the E. coli CLC, revealing how the molecular machine works. Replicative sliding clamp loading is critical for DNA replication and repair. Here, authors report structures of major clamp loading intermediates in a bacterial system, revealing how the clamp is opened and loaded onto DNA.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-52623-9