View source for 8pdk


==X-ray structure of the Thermus thermophilus PilF-GSPIIB domain in the c-di-GMP bound state==
<StructureSection load='8pdk' size='340' side='right'caption='[[8pdk]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8pdk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB27 Thermus thermophilus HB27]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8PDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PDK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8pdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pdk OCA], [https://pdbe.org/8pdk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pdk RCSB], [https://www.ebi.ac.uk/pdbsum/8pdk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pdk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PILB_THET8 PILB_THET8] ATPase component of the type IV pilus (T4P) that plays a role in surface and host cell adhesion, colonization, biofilm maturation, virulence, and twitching, a form of surface-associated motility facilitated by cycles of extension, adhesion, and retraction of T4P fibers (By similarity) (PubMed:29717025). Acts as a molecular motor to provide the energy that is required for biogenesis of the pilus and the extrusion of substrates generated in the cytoplasm (PubMed:27667690). PilB ATPase activity is also essential for T4P extension while antagonist PilT ATPase activity is required for T4P retraction (By similarity).[UniProtKB:P22608][UniProtKB:Q1D098]<ref>PMID:27667690</ref> <ref>PMID:29717025</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
c-di-GMP is an important second messenger in bacteria regulating, for example motility, biofilm formation, cell wall biosynthesis, infectivity, and natural transformability. It binds to a multitude of intracellular receptors. This includes proteins containing general secretory pathway II (GSPII) domains such as the N-terminal domain of the Vibrio cholerae ATPase MshE (MshEN) which binds c-di-GMP with two copies of a 24-amino acids sequence motif. The traffic ATPase PilF from Thermus thermophilus is important for type IV pilus biogenesis, twitching motility, surface attachment, and natural DNA-uptake and contains three consecutive homologous GPSII domains. We show that only two of these domains bind c-di-GMP and define the structural basis for the exceptional high affinity of the GSPII-B domain for c-di-GMP, which is 83-fold higher than that of the prototypical MshEN domain. Our work establishes an extended consensus sequence for the c-di-GMP-binding motif and highlights the role of hydrophobic residues for high-affinity recognition of c-di-GMP. Our structure is the first example for a c-di-GMP-binding domain not relying on arginine residues for ligand recognition. We also show that c-di-GMP-binding induces local unwinding of an alpha-helical turn as well as subdomain reorientation to reinforce intermolecular contacts between c-di-GMP and the C-terminal subdomain. Abolishing c-di-GMP binding to GSPII-B reduces twitching motility and surface attachment but not natural DNA-uptake. Overall, our work contributes to a better characterization of c-di-GMP binding in this class of effector domains, allows the prediction of high-affinity c-di-GMP-binding family members, and advances our understanding of the importance of c-di-GMP binding for T4P-related functions.

The structural basis for high-affinity c-di-GMP binding to the GSPII-B domain of the traffic ATPase PilF from Thermus thermophilus.,Neissner K, Keller H, Kirchner L, Dusterhus S, Duchardt-Ferner E, Averhoff B, Wohnert J J Biol Chem. 2024 Nov 29;301(1):108041. doi: 10.1016/j.jbc.2024.108041. PMID:39615687<ref>PMID:39615687</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8pdk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thermus thermophilus HB27]]
[[Category: Neissner K]]
[[Category: Woehnert J]]