An α Helix to β Barrel Domain Switch Transforms the Transcription Factor RfaH into a Translation Factor

Burmann, Björn M.; Knauer, Stefan H.; Sevostyanova, Anastasia; Schweimer, Kristian; Mooney, Rachel A.; Landick, Robert; Artsimovitch, Irina; Rösch, Paul

doi:10.1016/j.cell.2012.05.042

Cited by 220 publications

(542 citation statements)

References 56 publications

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“…Sometimes it takes an additional factor to stabilize an alternative structure, such as a change in the solvent conditions or a binding event (e.g. [181][182][183][184]). …”

Section: Multi-basin Folding Landscapes Allostery and Conformationalmentioning

confidence: 99%

Biophysics of protein evolution and evolutionary protein biophysics

Sikosek

Chan

2014

J. R. Soc. Interface.

219

207

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The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence-structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by 'hidden' conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution.

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“…Sometimes it takes an additional factor to stabilize an alternative structure, such as a change in the solvent conditions or a binding event (e.g. [181][182][183][184]). …”

Section: Multi-basin Folding Landscapes Allostery and Conformationalmentioning

confidence: 99%

Biophysics of protein evolution and evolutionary protein biophysics

Sikosek

Chan

2014

J. R. Soc. Interface.

219

207

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“…77,78 This is consistent with the hypothesis that such bistable structures may function as evolutionary bridges between proteins carrying out different functions, supported by recent experimental and theoretical work. [79][80][81][82] In addition, several natural examples exist of proteins that populate different native states in the presence of different binding partners [83][84][85] and are not intrinsically disordered, indicating that this is not a property unique to IDPs. Nonetheless, it is likely to be easier for nature to design IDPs to bind in different structures, because of the larger contribution made by the binding interface to the overall stability.…”

Section: B Binding Transition Pathsmentioning

confidence: 99%

Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model

Knott

Best

2014

The Journal of Chemical Physics

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Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an "induced fit" or "conformational selection" mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD. © 2014 AIP Publishing LLC.

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“…Overproduction of RfaH, however, increased the production of capsular polysaccharide in E. coli K4 (Cimini et al, 2013). Furthermore, in E. coli, RfaH and NusG are known to interact with the ribosomal protein S10 coupling transcription with translation (Burmann et al, 2010(Burmann et al, , 2012NandyMazumdar & Artsimovitch, 2015). RfaH was also implicated in regulation on the post-transcriptional level by affecting the function of small RNA MicA (Moores et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Expression of the Yersinia enterocolitica O:3 LPS O-antigen and outer core gene clusters is RfaH-dependent

Leskinen

Varjosalo

et al. 2015

Microbiology

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The antiterminator RfaH is required for the expression of LPS, capsule, haemolysin, exotoxin, haemin uptake receptor and F pilus. As these structures are critical for bacterial virulence, loss of RfaH usually leads to attenuation. Here, we inactivated the rfaH gene of Yersinia enterocolitica O:3 to study its role in this enteropathogen. RNA sequencing of the WT and DrfaH strain transcriptomes revealed that RfaH acted as a highly specific regulator that enhanced the transcription of the operons involved in biosynthesis of LPS O-antigen and outer core (OC), but did not affect the expression of enterobacterial common antigen. Interestingly, the transcriptome of the DrfaH strain was very similar to that of an O-antigen-negative mutant. This indicated that some of the changes seen in the DrfaH strain, such as the genes involved in outer membrane homeostasis or in the stress-response-associated Cpx pathway, were actually due to indirect responses via the loss of O-antigen. The decreased amount of LPS on the DrfaH strain cell surface resulted in an attenuated stress response, and lower resistance to compounds such as SDS and polymyxin B. However, the DrfaH strain was significantly more resistant to complement-mediated killing by normal human serum. Taken together, our results revealed a novel role of RfaH acting as a highly specific regulator of O-antigen and OC of LPS in Y. enterocolitica O:3. It may be speculated that RfaH might have an in vivo role in controlling tissue-specific expression of bacterial surface oligo/polysaccharides.

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An α Helix to β Barrel Domain Switch Transforms the Transcription Factor RfaH into a Translation Factor

Cited by 220 publications

References 56 publications

Biophysics of protein evolution and evolutionary protein biophysics

Biophysics of protein evolution and evolutionary protein biophysics

Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model

Expression of the Yersinia enterocolitica O:3 LPS O-antigen and outer core gene clusters is RfaH-dependent

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