Transformation

Knauer, Stefan H.; Rösch, Paul; Artsimovitch, Irina

doi:10.4161/rna.22724

Cited by 12 publications

(13 citation statements)

References 35 publications

(47 reference statements)

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“…Although transient intra- or intermolecular NTD:CTD interactions might occur in all NusG proteins, only tmNusG has developed additional features to stabilize the autoinhibited state. However, in contrast to the ecNusG paralog RfaH, autoinhibition in tmNusG appears to merely support thermostability and has no regulatory role (11,41–42). …”

Section: Resultsmentioning

confidence: 95%

Thermotoga maritimaNusG: domain interaction mediates autoinhibition and thermostability

et al. 2016

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NusG, the only universally conserved transcription factor, comprises an N- and a C-terminal domain (NTD, CTD) that are flexibly connected and move independently in Escherichia coli and other organisms. In NusG from the hyperthermophilic bacterium Thermotoga maritima (tmNusG), however, NTD and CTD interact tightly. This closed state stabilizes the CTD, but masks the binding sites for the interaction partners Rho, NusE and RNA polymerase (RNAP), suggesting that tmNusG is autoinhibited. Furthermore, tmNusG and some other bacterial NusGs have an additional domain, DII, of unknown function. Here we demonstrate that tmNusG is indeed autoinhibited and that binding to RNAP may stabilize the open conformation. We identified two interdomain salt bridges as well as Phe336 as major determinants of the domain interaction. By successive weakening of this interaction we show that after domain dissociation tmNusG-CTD can bind to Rho and NusE, similar to the Escherichia coli NusG-CTD, indicating that these interactions are conserved in bacteria. Furthermore, we show that tmNusG-DII interacts with RNAP as well as nucleic acids with a clear preference for double stranded DNA. We suggest that tmNusG-DII supports tmNusG recruitment to the transcription elongation complex and stabilizes the tmNusG:RNAP complex, a necessary adaptation to high temperatures.

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Section: Resultsmentioning

confidence: 95%

Thermotoga maritimaNusG: domain interaction mediates autoinhibition and thermostability

et al. 2016

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“…In the case of CLIC1, a chloride ion channel protein, an all‐α N‐terminal domain acts as a channel protein, but it can also show an stable α3+β4 arrangement of still unknown activity . Another example is the RfaH protein (defined as a transformer protein; Figure B), the C‐terminal domain of which possesses an all‐β open structure, which acquires the capability to recruit the RNA polymerase and the ribosome, and an all‐α closed structure that autoinhibits recruitment to the selected targets . In the case of XCL1, a chemokine showing the structural arrangement typical of this class of proteins, it can experience a structural transition to a β‐sheet form to gain glycosaminoglycan binding capacity .…”

Section: Metamorphic Proteinsmentioning

confidence: 99%

“…This states that, under native conditions, a protein uniquely folds into the three‐dimensional structure with the lowest Gibbs energy of the system, which is fully encoded in its amino acid sequence. For many years, this hypothesis has been oversimplified to the “one sequence, one structure, one function” canon …”

Section: Introductionmentioning

confidence: 99%

“…Generally, each native structure shows different functionality . The term “transformer protein” has been proposed for extreme cases of metamorphism, in which the structures are completely different, such as the C‐terminal domain of RfaH (CtD; Figure B) …”

Section: Introductionmentioning

confidence: 99%

“…A chameleon sequence (Figure D) is an amino acid sequence that can adopt different secondary structures, depending on the protein in which it is found …”

Section: Introductionmentioning

confidence: 99%

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Turncoat Polypeptides: We Adapt to Our Environment

et al. 2019

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A common interpretation of Anfinsen's hypothesis states that one amino acid sequence should fold into a single, native, ordered state, or a highly similar set thereof, coinciding with the global minimum in the folding‐energy landscape, which, in turn, is responsible for the function of the protein. However, this classical view is challenged by many proteins and peptide sequences, which can adopt exchangeable, significantly dissimilar conformations that even fulfill different biological roles. The similarities and differences of concepts related to these proteins, mainly chameleon sequences, metamorphic proteins, and switch peptides, which are all denoted herein “turncoat” polypeptides, are reviewed. As well as adding a twist to the conventional view of protein folding, the lack of structural definition adds clear versatility to the activity of proteins and can be used as a tool for protein design and further application in biotechnology and biomedicine.

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A polymetamorphic protein

et al. 2013

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Arc repressor is a homodimeric protein with a ribbon-helix-helix fold. A single polar-tohydrophobic substitution (N11L) at a solvent-exposed position leads to population of an alternate dimeric fold in which 3 10 helices replace a b-sheet. Here we find that the variant Q9V/N11L/R13V (S-VLV), with two additional polar-to-hydrophobic surface mutations in the same b-sheet, forms a highly stable, reversibly folded octamer with approximately half the©a-helical content of wild-type Arc. At low protein concentration and low ionic strength, S-VLV also populates both dimeric topologies previously observed for N11L, as judged by NMR chemical shift comparisons. Thus, accumulation of simple hydrophobic mutations in Arc progressively reduces fold specificity, leading first to a sequence with two folds and then to a manifold bridge sequence with at least three different topologies. Residues 9-14 of S-VLV form a highly hydrophobic stretch that is predicted to be amyloidogenic, but we do not observe aggregates of higher order than octamer. Increases in sequence hydrophobicity can promote amyloid aggregation but also exert broader and more complex effects on fold specificity. Altered native folds, changes in fold coupled to oligomerization, toxic pre-amyloid oligomers, and amyloid fibrils may represent a near continuum of accessible alternatives in protein structure space.

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Transformation

Cited by 12 publications

References 35 publications

Thermotoga maritimaNusG: domain interaction mediates autoinhibition and thermostability

Thermotoga maritimaNusG: domain interaction mediates autoinhibition and thermostability

Turncoat Polypeptides: We Adapt to Our Environment

A polymetamorphic protein

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