6sft: Difference between revisions
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==Solution structure of protein ARR_CleD in complex with c-di-GMP== | ==Solution structure of protein ARR_CleD in complex with c-di-GMP== | ||
<StructureSection load='6sft' size='340' side='right'caption='[[6sft]]' scene=''> | <StructureSection load='6sft' size='340' side='right'caption='[[6sft]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full | <table><tr><td colspan='2'>[[6sft]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cauvn Cauvn]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SFT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SFT FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sft OCA], [http://pdbe.org/6sft PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sft RCSB], [http://www.ebi.ac.uk/pdbsum/6sft PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sft ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C2E:9,9-[(2R,3R,3aS,5S,7aR,9R,10R,10aS,12S,14aR)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d 3,2-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecine-2,9-diyl]bis(2-amino-1,9-dihydro-6H-purin-6-one)'>C2E</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cleD, CCNA_03198 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=565050 CAUVN])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sft OCA], [http://pdbe.org/6sft PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sft RCSB], [http://www.ebi.ac.uk/pdbsum/6sft PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sft ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The bacterial second messenger cyclic diguanylate (c-di-GMP) regulates a wide range of cellular functions from biofilm formation to growth and survival. Targeting a second-messenger network is challenging because the system involves a multitude of components with often overlapping functions. Here, we present a strategy to intercept c-di-GMP signaling pathways by directly targeting the second messenger. For this, we developed a c-di-GMP-sequestering peptide (CSP) that was derived from a CheY-like c-di-GMP effector protein. CSP binds c-di-GMP with submicromolar affinity. The elucidation of the CSPc-di-GMP complex structure by NMR identified a linear c-di-GMP-binding motif, in which a self-intercalated c-di-GMP dimer is tightly bound by a network of H bonds and pi-stacking interactions involving arginine and aromatic residues. Structure-based mutagenesis yielded a variant with considerably higher, low-nanomolar affinity, which subsequently was shortened to 19 residues with almost uncompromised affinity. We demonstrate that endogenously expressed CSP intercepts c-di-GMP signaling and effectively inhibits biofilm formation in Pseudomonas aeruginosa, the most widely used model for serious biofilm-associated medical implications. | |||
Intercepting second-messenger signaling by rationally designed peptides sequestering c-di-GMP.,Hee CS, Habazettl J, Schmutz C, Schirmer T, Jenal U, Grzesiek S Proc Natl Acad Sci U S A. 2020 Jul 21;117(29):17211-17220. doi:, 10.1073/pnas.2001232117. Epub 2020 Jul 1. PMID:32611811<ref>PMID:32611811</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6sft" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Cauvn]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Grzesiek S]] | [[Category: Grzesiek, S]] | ||
[[Category: Habazettl J]] | [[Category: Habazettl, J]] | ||
[[Category: Hee | [[Category: Hee, C S]] | ||
[[Category: Jenal U]] | [[Category: Jenal, U]] | ||
[[Category: Schirmer T]] | [[Category: Schirmer, T]] | ||
[[Category: C-di-gmp]] | |||
[[Category: Chey]] | |||
[[Category: Cled]] | |||
[[Category: Response regulator]] | |||
[[Category: Signaling protein]] | |||
Revision as of 05:59, 20 January 2021
Solution structure of protein ARR_CleD in complex with c-di-GMP
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