Topological constraints and modular structure in the folding and functional motions of GlpG, an intramembrane protease
Identifieur interne : 000007 ( Main/Exploration ); 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
Affiliations:
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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. 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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><affiliations><list><country><li>Danemark</li></country></list><tree><noCountry><name sortKey="Truong, Ha H" sort="Truong, Ha H" uniqKey="Truong H" first="Ha H." last="Truong">Ha H. Truong</name><name sortKey="Wolynes, Peter G" sort="Wolynes, Peter G" uniqKey="Wolynes P" first="Peter G." last="Wolynes">Peter G. Wolynes</name></noCountry><country name="Danemark"><noRegion><name sortKey="Schafer, Nicholas P" sort="Schafer, Nicholas P" uniqKey="Schafer N" first="Nicholas P." last="Schafer">Nicholas P. Schafer</name></noRegion><name sortKey="Lindorff Larsen, Kresten" sort="Lindorff Larsen, Kresten" uniqKey="Lindorff Larsen K" first="Kresten" last="Lindorff-Larsen">Kresten Lindorff-Larsen</name><name sortKey="Otzen, Daniel E" sort="Otzen, Daniel E" uniqKey="Otzen D" first="Daniel E." last="Otzen">Daniel E. Otzen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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