Structural modules of the stress-induced protein HflX: an outlook on its evolution and biological role.

Krishnamoorthi Srinivasan, Sandip Dey, Jayati Sengupta

Current genetics 2019 Apr

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Multifunctional proteins often show modular structures. A functional domain and the structural modules within the domain show evolutionary conservation of their spatial arrangement since that gives the protein its functionality. However, the question remains as to how members of different domains of life (Archaea, Bacteria, Eukarya), polish and perfect these modules within conserved multidomain proteins, to tailor functional proteins according to their specific requirements. In the quest for plausible answers to this question, we studied the bacterial protein HflX. HflX is a universally conserved member of the Obg-GTPase superfamily but its functional role in Archaea and Eukarya is barely known. It is a multidomain protein and possesses, in addition to its conserved GTPase domain, an ATP-binding N-terminal domain. It is involved in heat stress response in Escherichia coli and our laboratory recently identified an ATP-dependent RNA helicase activity of E. coli HflX, which is likely instrumental in rescuing ribosomes during heat stress. Because perception and response to stress is expected to be different in different life forms, the question is whether this activity is preserved in higher organisms or not. Thus, we explored the evolution pattern of different structural modules of HflX, with particular emphasis on the ATP-binding domain, to understand plausible biological role of HflX in other forms of life. Our analyses indicate that, while the evolutionary pattern of the GTPase domain follows a conserved phylogeny, conservation of the ATP-binding domain shows a complicated pattern. The limited analysis described here hints towards possible evolutionary adaptations and modifications of the domain, something which needs to be investigated in more depth in homologs from other life forms. Deciphering how nature 'tweaks' such modules, both structurally and functionally, may help in understanding the evolution of such proteins, and, on a large-scale, of stress-related proteins in general as well.

Citation

Krishnamoorthi Srinivasan, Sandip Dey, Jayati Sengupta. Structural modules of the stress-induced protein HflX: an outlook on its evolution and biological role. Current genetics. 2019 Apr;65(2):363-370