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(p)ppGpp controls stringent factors by exploiting antagonistic allosteric coupling between catalytic domains

Roghanian, Mohammad (author)
Umeå University,Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
Van Nerom, Katleen (author)
Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles, Campus La Plaine, Boulevard du Triomphe, Brussels, Belgium
Takada, Hiraku (author)
Umeå University,Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
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Caballero-Montes, Julien (author)
Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles, Campus La Plaine, Boulevard du Triomphe, Brussels, Belgium
Tamman, Hedvig (author)
Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles, Campus La Plaine, Boulevard du Triomphe, Brussels, Belgium
Kudrin, Pavel (author)
University of Tartu, Institute of Technology, Tartu, Estonia
Talavera, Ariel (author)
Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles, Campus La Plaine, Boulevard du Triomphe, Brussels, Belgium
Dzhygyr, Ievgen (author)
Umeå University,Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
Ekström, Simon (author)
Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Masspektrometri,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,BioMS,Forskargrupper vid Lunds universitet,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Mass Spectrometry,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
Atkinson, Gemma C. (author)
Umeå University,Lund University,Lunds universitet,Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Experimental Medical Science, Lund University, Lund, Sweden,Proteinevolution,Forskargrupper vid Lunds universitet,Protein Evolution,Lund University Research Groups
Garcia-Pino, Abel (author)
Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles, Campus La Plaine, Boulevard du Triomphe, Brussels, Belgium; WELBIO, Avenue Hippocrate 75, Brussels, Belgium
Hauryliuk, Vasili, 1980- (author)
Umeå University,Lund University,Lunds universitet,Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),University of Tartu, Institute of Technology, Tartu, Estonia; Department of Experimental Medical Science, Lund University, Lund, Sweden,Molekylär enzymologi,Forskargrupper vid Lunds universitet,Molecular Enzymology,Lund University Research Groups
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 (creator_code:org_t)
Elsevier, 2021
2021
English.
In: Molecular Cell. - : Elsevier. - 1097-2765 .- 1097-4164. ; 81:16, s. 3310-3322.e6
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Amino acid starvation is sensed by Escherichia coli RelA and Bacillus subtilis Rel through monitoring the aminoacylation status of ribosomal A-site tRNA. These enzymes are positively regulated by their product—the alarmone nucleotide (p)ppGpp—through an unknown mechanism. The (p)ppGpp-synthetic activity of Rel/RelA is controlled via auto-inhibition by the hydrolase/pseudo-hydrolase (HD/pseudo-HD) domain within the enzymatic N-terminal domain region (NTD). We localize the allosteric pppGpp site to the interface between the SYNTH and pseudo-HD/HD domains, with the alarmone stimulating Rel/RelA by exploiting intra-NTD autoinhibition dynamics. We show that without stimulation by pppGpp, starved ribosomes cannot efficiently activate Rel/RelA. Compromised activation by pppGpp ablates Rel/RelA function in vivo, suggesting that regulation by the second messenger (p)ppGpp is necessary for mounting an acute starvation response via coordinated enzymatic activity of individual Rel/RelA molecules. Control by (p)ppGpp is lacking in the E. coli (p)ppGpp synthetase SpoT, thus explaining its weak synthetase activity.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

(p)ppGpp
allostery
Hydrogen-Deuterium exchange Mass Spectrometry
positive feedback regulation
Rel
RelA
RelA-SpoT Homolog
ribosome
SpoT
stringent response

Publication and Content Type

ref (subject category)
art (subject category)

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