A survey of HK, HPt, and RR domains and their organization in two-component systems and phosphorelay proteins of organisms with fully sequenced genomes

Abstract

Two Component Systems and Phosphorelays (TCS/PR) are environmental signal transduction cascades in prokaryotes and, less frequently, in eukaryotes. The internal domain organization of proteins and the topology of TCS/PR cascades play an important role in shaping the responses of the circuits. It is thus important to maintain updated censuses of TCS/PR proteins in order to identify the various topologies used by nature and enable a systematic study of the dynamics associated with those topologies. To create such a census, we analyzed the proteomes of 7,609 organisms from all domains of life with fully sequenced and annotated genomes. To begin, we survey each proteome searching for proteins containing domains that are associated with internal signal transmission within TCS/PR: Histidine Kinase (HK), Response Regulator (RR) and Histidine Phosphotranfer (HPt) domains, and analyze how these domains are arranged in the individual proteins. Then, we find all types of operon organization and calculate how much more likely are proteins that contain TCS/PR domains to be coded by neighboring genes than one would expect from the genome background of each organism. Finally, we analyze if the fusion of domains into single TCS/PR proteins is more frequently observed than one might expect from the background of each proteome. We find 50 alternative ways in which the HK, HPt, and RR domains are observed to organize into single proteins. In prokaryotes, TCS/PR coding genes tend to be clustered in operons. 90% of all proteins identified in this study contain just one of the three domains, while 8% of the remaining proteins combine one copy of an HK, a RR, and/or an HPt domain. In eukaryotes, 25% of all TCS/PR proteins have more than one domain. These results might have implications for how signals are internally transmitted within TCS/PR cascades. These implications could explain the selection of the various designs in alternative circumstances.

What influences selection of native phosphorelay architectures?

“…To address this question we used a comprehensive census of PR circuit architectures, and analyzed over 9000 fully sequenced microbial and plant genomes. We found that more than 72% of all PR coded in a single operon have the same circuit architecture (M3 of Figure 1) 16 . Four additional architectures account for another 27% of all other PR (architectures M1, M2, M2', an M4 of Figure 1) 16 .…”

“…In the case of PR, a specific architecture is observed in over 72% of all genomic PR 16 in a sample of more than 9000 organisms 4 . This suggested that indeed there could be design principles for selecting the architecture of these circuits.…”

“…PR shown in Figure 1 represent more than 99% of all PR circuits present in the fully sequenced genomes of more than 9000 organisms. This information was obtained from 4 . Two types of models were created for each architecture.…”

“…Phosphorelays (PR) are a large and important class of signal transduction circuits in microorganisms and some plants [1][2][3][4] . A self-phosphorylating Sensor Kinase (SK) modulates its own phosphorylation state in response to the environmental signal.…”

“…Still, PR circuits can assemble the four-step phosphotransfer cascade using alternative protein domain assembly architectures [12][13][14][16][17][18] . This raises the question of whether alternative PR architectures may have irreducible physiological differences for the behavior of the circuit or if those differences may be quenched easily by evolving appropriate parameter values 9,10,[19][20][21] .…”