Topological constraints and modular structure in the folding and functional motions of GlpG, an intramembrane protease
Identifieur interne : 000007 ( Main/Merge ); précédent : 000006; suivant : 000008Topological constraints and modular structure in the folding and functional motions of GlpG, an intramembrane protease
Auteurs : Nicholas P. Schafer [Danemark] ; Ha H. Truong ; Daniel E. Otzen [Danemark] ; Kresten Lindorff-Larsen [Danemark] ; Peter G. WolynesSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2016.
Abstract
Membrane proteins perform diverse functions in the cell while being embedded in lipid bilayers, but the presence of the anisotropic, nonpolar membrane environment has slowed progress in understanding how these proteins fold and function. Herein, we study GlpG, an intramembrane protease, using computationally efficient models to fill in structural details that are currently invisible to experimental techniques and inaccessible to atomistic simulations. We find that GlpG’s modular functional architecture leaves an imprint throughout its folding and functional landscape, leading to multiple possible folding pathways and the population of near-native states with functional significance. We propose a mechanism by which destabilizing mutations can accelerate folding in detergent micelles, a previously puzzling experimental observation.
Url:
DOI: 10.1073/pnas.1524027113
PubMed: 26858402
PubMed Central: 4776503
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000104
- to stream Pmc, to step Curation: 000104
- to stream Pmc, to step Checkpoint: 000005
- to stream Ncbi, to step Merge: 000709
- to stream Ncbi, to step Curation: 000709
- to stream Ncbi, to step Checkpoint: 000709
Links to Exploration step
PMC:4776503Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Topological constraints and modular structure in the folding and functional motions of GlpG, an intramembrane protease</title>
<author><name sortKey="Schafer, Nicholas P" sort="Schafer, Nicholas P" uniqKey="Schafer N" first="Nicholas P." last="Schafer">Nicholas P. Schafer</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Interdisciplinary Nanoscience Center, Department of Molecular Biology and Genetics,<institution>Aarhus University</institution>
, DK-8000 Aarhus,<country>Denmark</country>
;</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Truong, Ha H" sort="Truong, Ha H" uniqKey="Truong H" first="Ha H." last="Truong">Ha H. Truong</name>
<affiliation><nlm:aff id="aff2">Department of Chemistry, Center for Theoretical Biological Physics,<institution>Rice University</institution>
, Houston,<addr-line>TX</addr-line>
77005;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Otzen, Daniel E" sort="Otzen, Daniel E" uniqKey="Otzen D" first="Daniel E." last="Otzen">Daniel E. Otzen</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Interdisciplinary Nanoscience Center, Department of Molecular Biology and Genetics,<institution>Aarhus University</institution>
, DK-8000 Aarhus,<country>Denmark</country>
;</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lindorff Larsen, Kresten" sort="Lindorff Larsen, Kresten" uniqKey="Lindorff Larsen K" first="Kresten" last="Lindorff-Larsen">Kresten Lindorff-Larsen</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">The Linderstrøm-Lang Centre for Protein Science, Department of Biology,<institution>University of Copenhagen</institution>
, DK-2200 Copenhagen,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wolynes, Peter G" sort="Wolynes, Peter G" uniqKey="Wolynes P" first="Peter G." last="Wolynes">Peter G. Wolynes</name>
<affiliation><nlm:aff id="aff2">Department of Chemistry, Center for Theoretical Biological Physics,<institution>Rice University</institution>
, Houston,<addr-line>TX</addr-line>
77005;</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">26858402</idno>
<idno type="pmc">4776503</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776503</idno>
<idno type="RBID">PMC:4776503</idno>
<idno type="doi">10.1073/pnas.1524027113</idno>
<date when="2016">2016</date>
<idno type="wicri:Area/Pmc/Corpus">000104</idno>
<idno type="wicri:Area/Pmc/Curation">000104</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000005</idno>
<idno type="wicri:Area/Ncbi/Merge">000709</idno>
<idno type="wicri:Area/Ncbi/Curation">000709</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000709</idno>
<idno type="wicri:doubleKey">0027-8424:2016:Schafer N:topological:constraints:and</idno>
<idno type="wicri:Area/Main/Merge">000007</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Topological constraints and modular structure in the folding and functional motions of GlpG, an intramembrane protease</title>
<author><name sortKey="Schafer, Nicholas P" sort="Schafer, Nicholas P" uniqKey="Schafer N" first="Nicholas P." last="Schafer">Nicholas P. Schafer</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Interdisciplinary Nanoscience Center, Department of Molecular Biology and Genetics,<institution>Aarhus University</institution>
, DK-8000 Aarhus,<country>Denmark</country>
;</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Truong, Ha H" sort="Truong, Ha H" uniqKey="Truong H" first="Ha H." last="Truong">Ha H. Truong</name>
<affiliation><nlm:aff id="aff2">Department of Chemistry, Center for Theoretical Biological Physics,<institution>Rice University</institution>
, Houston,<addr-line>TX</addr-line>
77005;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Otzen, Daniel E" sort="Otzen, Daniel E" uniqKey="Otzen D" first="Daniel E." last="Otzen">Daniel E. Otzen</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Interdisciplinary Nanoscience Center, Department of Molecular Biology and Genetics,<institution>Aarhus University</institution>
, DK-8000 Aarhus,<country>Denmark</country>
;</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lindorff Larsen, Kresten" sort="Lindorff Larsen, Kresten" uniqKey="Lindorff Larsen K" first="Kresten" last="Lindorff-Larsen">Kresten Lindorff-Larsen</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">The Linderstrøm-Lang Centre for Protein Science, Department of Biology,<institution>University of Copenhagen</institution>
, DK-2200 Copenhagen,<country>Denmark</country>
</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wolynes, Peter G" sort="Wolynes, Peter G" uniqKey="Wolynes P" first="Peter G." last="Wolynes">Peter G. Wolynes</name>
<affiliation><nlm:aff id="aff2">Department of Chemistry, Center for Theoretical Biological Physics,<institution>Rice University</institution>
, Houston,<addr-line>TX</addr-line>
77005;</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="ISSN">0027-8424</idno>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Significance</title>
<p>Membrane proteins perform diverse functions in the cell while being embedded in lipid bilayers, but the presence of the anisotropic, nonpolar membrane environment has slowed progress in understanding how these proteins fold and function. Herein, we study GlpG, an intramembrane protease, using computationally efficient models to fill in structural details that are currently invisible to experimental techniques and inaccessible to atomistic simulations. We find that GlpG’s modular functional architecture leaves an imprint throughout its folding and functional landscape, leading to multiple possible folding pathways and the population of near-native states with functional significance. We propose a mechanism by which destabilizing mutations can accelerate folding in detergent micelles, a previously puzzling experimental observation.</p>
</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Ticri/CIDE/explor/CyberinfraV1/Data/Main/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000007 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Merge/biblio.hfd -nk 000007 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Ticri/CIDE |area= CyberinfraV1 |flux= Main |étape= Merge |type= RBID |clé= PMC:4776503 |texte= Topological constraints and modular structure in the folding and functional motions of GlpG, an intramembrane protease }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Merge/RBID.i -Sk "pubmed:26858402" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Merge/biblio.hfd \ | NlmPubMed2Wicri -a CyberinfraV1
![]() | This area was generated with Dilib version V0.6.25. | ![]() |