title: A NusG paralogue from Mycobacterium tuberculosis, Rv0639, has evolved to interact with ribosomal protein S10 (Rv0700) but not to function as a transcription elongation-termination factor.
abstract: NusG, a well-conserved protein in all the three forms of life, is involved in transcription elongation and termination, as well as in the process of transcription-translation coupling. The existence of species-specific functional, as well as conformational, divergences in NusG makes it an attractive transcription factor to study, especially if it originates from a pathogen. Here, we report functional and conformational characterizations of the Mycobacterium tuberculosis (Mtb) protein Rv0639 that has been annotated as a homologue of Escherichia coli NusG. Rv0639 failed to complement the in vivo functions of E. coli NusG (Ec NusG) and did not exhibit any signature of a transcription elongation-termination factor. However, it retained the ability to bind to its cognate ribosomal protein S10 (Rv0700). Compared with Ec NusG, Rv0639 possesses unique conformational features characterized by altered secondary structures in the C-terminal domain (CTD), an unusually long and disordered linker region between the N-terminal domain (NTD) and CTD, and a folding of its NTD over its CTD. This unusual folded conformation could have imparted specialized functions to this protein, required to adapt the physiology of Mtb. We speculate that in the absence of a bona fide RfaH, a NusG paralogue that is involved in pathogenicity in E. coli, Rv0639 functions as an RfaH-like factor and is involved in pathogenicity using unidentified ops-like sequences in the Mtb genome. And hence, we reannotate Rv0639 as a paralogue of NusG, instead of a homologue.
authors.affiliation: Laboratory of Transcription, Center for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad-500 001, India.
authors.forename: B Sudha
authors.initials: BS
authors.lastname: Kalyani
authors.affiliation: Laboratory of Transcription, Center for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad-500 001, India.
authors.forename: Radhika
authors.initials: R
authors.lastname: Kunamneni
authors.affiliation: Laboratory of Transcription, Center for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad-500 001, India.
authors.forename: Megha
authors.initials: M
authors.lastname: Wal
authors.affiliation: Laboratory of Transcription, Center for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad-500 001, India.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Ranjan
authors.affiliation: Laboratory of Transcription, Center for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad-500 001, India.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Sen
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D008958:Models, Molecular; D008970:Molecular Weight; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D012234:Rho Factor / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D012234:Rho Factor; D012269:Ribosomal Proteins; C029537:ribosomal protein S10