The bacterial DNA sliding clamp, β-clamp: structure, interactions, dynamics and drug discovery.

Autor: Simonsen S; Linderstrøm-Lang Centre for Protein Science, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark.; Structural Biology and NMR Laboratory, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark., Søgaard CK; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway., Olsen JG; Linderstrøm-Lang Centre for Protein Science, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark.; Structural Biology and NMR Laboratory, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark.; Department of Biology, REPIN, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark., Otterlei M; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. marit.otterlei@ntnu.no., Kragelund BB; Linderstrøm-Lang Centre for Protein Science, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark. bbk@bio.ku.dk.; Structural Biology and NMR Laboratory, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark. bbk@bio.ku.dk.; Department of Biology, REPIN, University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark. bbk@bio.ku.dk.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 May 30; Vol. 81 (1), pp. 245. Date of Electronic Publication: 2024 May 30.
DOI: 10.1007/s00018-024-05252-w
Abstrakt: DNA replication is a tightly coordinated event carried out by a multiprotein replication complex. An essential factor in the bacterial replication complex is the ring-shaped DNA sliding clamp, β-clamp, ensuring processive DNA replication and DNA repair through tethering of polymerases and DNA repair proteins to DNA. β -clamp is a hub protein with multiple interaction partners all binding through a conserved clamp binding sequence motif. Due to its central role as a DNA scaffold protein, β-clamp is an interesting target for antimicrobial drugs, yet little effort has been put into understanding the functional interactions of β-clamp. In this review, we scrutinize the β-clamp structure and dynamics, examine how its interactions with a plethora of binding partners are regulated through short linear binding motifs and discuss how contexts play into selection. We describe the dynamic process of clamp loading onto DNA and cover the recent advances in drug development targeting β-clamp. Despite decades of research in β-clamps and recent landmark structural insight, much remains undisclosed fostering an increased focus on this very central protein.
(© 2024. The Author(s).)
Databáze: MEDLINE
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