Activation and polar sequestration of PopA, a c-di-GMP effector protein involved in Caulobacter crescentus cell cycle control

TY - JOUR

T1 - Activation and polar sequestration of PopA, a c-di-GMP effector protein involved in Caulobacter crescentus cell cycle control

AU - Ozaki, Shogo

AU - Schalch-Moser, Annina

AU - Zumthor, Ludwig

AU - Manfredi, Pablo

AU - Ebbensgaard, Anna

AU - Schirmer, Tilman

AU - Jenal, Urs

N1 - © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Summary: When Caulobacter crescentus enters S-phase the replication initiation inhibitor CtrA dynamically positions to the old cell pole to be degraded by the polar ClpXP protease. Polar delivery of CtrA requires PopA and the diguanylate cyclase PleD that positions to the same pole. Here we present evidence that PopA originated through gene duplication from its paralogue response regulator PleD and subsequent co-option as c-di-GMP effector protein. While the C-terminal catalytic domain (GGDEF) of PleD is activated by phosphorylation of the N-terminal receiver domain, functional adaptation has reversed signal transduction in PopA with the GGDEF domain adopting input function and the receiver domain serving as regulatory output. We show that the N-terminal receiver domain of PopA specifically interacts with RcdA, a component required for CtrA degradation. In contrast, the GGDEF domain serves to target PopA to the cell pole in response to c-di-GMP binding. In agreement with the divergent activation and targeting mechanisms, distinct markers sequester PleD and PopA to the old cell pole upon S-phase entry. Together these data indicate that PopA adopted a novel role as topology specificity factor to help recruit components of the CtrA degradation pathway to the protease specific old cell pole of C. crescentus.

AB - Summary: When Caulobacter crescentus enters S-phase the replication initiation inhibitor CtrA dynamically positions to the old cell pole to be degraded by the polar ClpXP protease. Polar delivery of CtrA requires PopA and the diguanylate cyclase PleD that positions to the same pole. Here we present evidence that PopA originated through gene duplication from its paralogue response regulator PleD and subsequent co-option as c-di-GMP effector protein. While the C-terminal catalytic domain (GGDEF) of PleD is activated by phosphorylation of the N-terminal receiver domain, functional adaptation has reversed signal transduction in PopA with the GGDEF domain adopting input function and the receiver domain serving as regulatory output. We show that the N-terminal receiver domain of PopA specifically interacts with RcdA, a component required for CtrA degradation. In contrast, the GGDEF domain serves to target PopA to the cell pole in response to c-di-GMP binding. In agreement with the divergent activation and targeting mechanisms, distinct markers sequester PleD and PopA to the old cell pole upon S-phase entry. Together these data indicate that PopA adopted a novel role as topology specificity factor to help recruit components of the CtrA degradation pathway to the protease specific old cell pole of C. crescentus.

KW - Bacterial Proteins/genetics

KW - Caulobacter crescentus/cytology

KW - Cell Cycle Checkpoints

KW - Cyclic GMP/analogs & derivatives

KW - Models, Molecular

KW - Phosphorylation

KW - Protein Binding

KW - Protein Conformation

KW - Protein Interaction Domains and Motifs

KW - Protein Processing, Post-Translational

U2 - 10.1111/mmi.12777

DO - 10.1111/mmi.12777

M3 - Journal article

C2 - 25171231

SN - 0950-382X

VL - 94

SP - 580

EP - 594

JO - Molecular Microbiology

JF - Molecular Microbiology

IS - 3

ER -