TY - JOUR

T1 - The bacterial DNA sliding clamp, β-clamp

T2 - structure, interactions, dynamics and drug discovery

AU - Simonsen, Signe

AU - Søgaard, Caroline K.

AU - Olsen, Johan G.

AU - Otterlei, Marit

AU - Kragelund, Birthe B.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

U2 - 10.1007/s00018-024-05252-w

DO - 10.1007/s00018-024-05252-w

M3 - Journal article

C2 - 38814467

VL - 81

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 1

M1 - 245

ER -