The Cellular Roles of the PII-like Protein SbtB and its Effector Molecule 3′,5′-c-di-Adenosine-5′-Monophosphate (c-di-AMP)

Abstract

The signaling transduction proteins of the PII superfamily, such as the PII-like protein SbtB, represent an ancient and exceptionally well-preserved protein family ubiquitously across all domains of life. Within cyanobacteria, SbtB serves as the main regulator of the carbon concentrating mechanism (CCM) and inorganic carbon (Ci) acclimation and is co-expressed from a bicistronic operon with the sodium-dependent bicarbonate transporter (SbtA). SbtB regulates bicarbonate uptake by direct interaction with all three cyanobacterial bicarbonate transporters: SbtA, BicA, and BCT1, in response to fluctuations in Ci levels and the adenylate energy charge (AEC). This study proposes a novel model for SbtB-mediated regulation of SbtA, emphasizing the significance of the flexible SbtB T-loop structure for this interaction, akin to the canonical PII T-loop in target protein interactions. In the AMP-bound state, corresponding to low Ci (LC) supply, SbtB inserts its T-loop into the inter-domain cleft of SbtA, inducing an inward-open conformation that facilitates substrate secretion into the cytoplasm while inhibiting backward bicarbonate transport. However, the cellular function of SbtB extends beyond bicarbonate uptake, significantly impacting central carbon metabolism and Ci acclimation. In the absence of SbtB in the slr1513 knockout mutant (ΔsbtB), CCM-associated gene expression, including the master Ci acclimation regulator NdhR, is broadly affected, resulting in a constitutively LC pre-acclimated state. In Synechocystis sp. PCC 6803, SbtB has been identified as the primary receptor of the second messenger, c-di-AMP. The SbtB:c-di-AMP complex regulates glycogen synthesis through its interaction with the glycogen branching enzyme (GlgB), which is essential for nighttime cyanobacterial survival. While SbtB primarily influences cellular functions related to the central carbon metabolism, c-di-AMP plays a multifaceted role in governing various cellular processes. These encompass the maintenance of ion homeostasis, notably K+ , Na+ , and Mg2+, thus regulating osmoprotection. C-di-AMP also exerts control over the central nitrogen metabolism, either directly or indirectly, by modulating the expression of NtcA, which in turn impacts on the process of chlorosis. Additionally, c-di-AMP plays a pivotal role in regulating the uptake of glutamine by regulating the activity of the basic amino acid and glutamine transporter complex BgtAB. Moreover, it is indispensable for facilitating chromatic acclimation by influencing the expression of CpcL through Rbp2.

Die Dissertation ist gesperrt bis zum 24. Juli 2027