Proposed Role for KaiC-Like ATPases as Major Signal Transduction Hubs in Archaea

Abstract

All organisms must adapt to ever-changing environmental conditions and accordingly have evolved diverse signal transduction systems. In bacteria, the most abundant networks are built around the two-component signal transduction systems that include histidine kinases and receiver domains. In contrast, eukaryotic signal transduction is dominated by serine/threonine/tyrosine protein kinases. Both of these systems are also found in archaea, but they are not as common and diversified as their bacterial and eukaryotic counterparts, suggesting the possibility that archaea have evolved other, still uncharacterized signal transduction networks. Here we propose a role for KaiC family ATPases, known to be key components of the circadian clock in cyanobacteria, in archaeal signal transduction. The KaiC family is notably expanded in most archaeal genomes, and although most of these ATPases remain poorly characterized, members of the KaiC family have been shown to control archaellum assembly and have been found to be a stable component of the gas vesicle system in Halobacteria. Computational analyses described here suggest that KaiC-like ATPases and their homologues with inactivated ATPase domains are involved in many other archaeal signal transduction pathways and comprise major hubs of complex regulatory networks. We predict numerous input and output domains that are linked to KaiC-like proteins, including putative homologues of eukaryotic DEATH domains that could function as adapters in archaeal signaling networks. We further address the relationships of the archaeal family of KaiC homologues to the bona fide KaiC of cyanobacteria and implications for the existence of a KaiCbased circadian clock apparatus in archaea.IMPORTANCE Little is currently known about signal transduction pathways in Archaea. Recent studies indicate that KaiC-like ATPases, known as key components of the circadian clock apparatus in cyanobacteria, are involved in the regulation of archaellum assembly and, likely, type IV pili and the gas vesicle system in Archaea. We performed comprehensive comparative genomic analyses of the KaiC family. A vast protein interaction network was revealed, with KaiC family proteins as hubs for numerous input and output components, many of which are shared with twocomponent signal transduction systems. Putative KaiC-based signal transduction systems are predicted to regulate the activities of membrane-associated complexes and individual proteins, such as signal recognition particle and membrane transporters, and also could be important for oxidative stress response regulation. KaiC-centered signal transduction networks are predicted to play major roles in archaeal physiology, and this work is expected to stimulate their experimental characterization.

Phyletic Distribution and Lineage-Specific Domain Architectures of Archaeal Two-Component Signal Transduction Systems

“…Studies on bacterial RRs revealed multiple instances where the REC domains were attached to standard metabolic enzymes, placing their activity under the environmental control ( 5 , 6 ). The same trend was noticed in archaea, in which some RRs contain an RadA-like NTPase of the KaiC family, the recently described archaeal signal transduction hubs ( 41 ), and several other predicted enzymes. All these fusions show narrow phyletic distributions, typically within a certain family or even a single genus of archaea.…”

“… b In archaea, see the respective Pfam entries for the complete listings. c iKaiC, inactivated KaiC-like ATPase domain (described in detail in reference 41 ). …”

“…All these fusions show narrow phyletic distributions, typically within a certain family or even a single genus of archaea. Thus, the KaiC-REC fusion is represented solely in the members of 6 genera ( Methanococcoides , Methanohalobium , Methanohalophilus , Methanolobus , Methanomethylovorans , and Methanosalsum ) of the family Methanosarcinaceae ( 41 ). Similarly, the fusion of one or two REC domains with the cellulose synthase (BcsA)-like glycosyltransferase domain (Pfam accession number PF13641), previously described in the Methanobacterium thermoautotrophicum protein MTH_548 ( 5 ), was detected only in Methanobacterium spp., Methanobrevibacter spp., and Methanothermobacter spp., three genera in the family Methanobacteriaceae ( Table 2 ).…”

“…HHpred searches show that NitrOD1 may be a variant of the Lrp/AsnC ligand-binding domain (Pfam ID PF01037), whereas NitrOD3 is related to the Roadblock/LC7 (Pfam ID PF03259) domain (Table S5). NitrOD2, NitrOD4, and NitrOD5 belong to the archaeal “Death domain-like” family ( 41 ).…”

Exploring the (Almost) Unknown: Archaeal Two-Component Systems

“…Among the archaeal REC-associated domains was the KaiC-like ATPase domain, known to be a key component of the circadian clock in cyanobacteria (24). In another recent article (25), the authors show that this domain is abundant and is present in most archaeal genomes, in contrast to its patchy phylogenetic distribution in bacteria. KaiC domain-containing proteins were frequently found to harbor characterized or potential input and output domains or domains known to participate in signaling processes.…”