View source for 6gjq


==human NBD1 of CFTR in complex with nanobody T27==
<StructureSection load='6gjq' size='340' side='right'caption='[[6gjq]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gjq]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GJQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GJQ 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]] 2.49&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</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=6gjq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gjq OCA], [https://pdbe.org/6gjq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gjq RCSB], [https://www.ebi.ac.uk/pdbsum/6gjq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gjq ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The leading cause of cystic fibrosis (CF) is the deletion of phenylalanine 508 (F508del) in the first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR). The mutation affects the thermodynamic stability of the domain and the integrity of the interface between NBD1 and the transmembrane domain leading to its clearance by the quality control system. Here, we develop nanobodies targeting NBD1 of human CFTR and demonstrate their ability to stabilize both isolated NBD1 and full-length protein. Crystal structures of NBD1-nanobody complexes provide an atomic description of the epitopes and reveal the molecular basis for stabilization. Furthermore, our data uncover a conformation of CFTR, involving detachment of NBD1 from the transmembrane domain, which contrast with the compact assembly observed in cryo-EM structures. This unexpected interface rearrangement is likely to have major relevance for CF pathogenesis but also for the normal function of CFTR and other ABC proteins.

Domain-interface dynamics of CFTR revealed by stabilizing nanobodies.,Sigoillot M, Overtus M, Grodecka M, Scholl D, Garcia-Pino A, Laeremans T, He L, Pardon E, Hildebrandt E, Urbatsch I, Steyaert J, Riordan JR, Govaerts C Nat Commun. 2019 Jun 14;10(1):2636. doi: 10.1038/s41467-019-10714-y. PMID:31201318<ref>PMID:31201318</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gjq" style="background-color:#fffaf0;"></div>

==See Also==
*[[ABC transporter 3D structures|ABC transporter 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Garcia-Pino A]]
[[Category: Govaerts C]]
[[Category: Grodecka M]]
[[Category: He L]]
[[Category: Hildebrandt E]]
[[Category: Laeremans T]]
[[Category: Overtus M]]
[[Category: Pardon E]]
[[Category: Riordan JR]]
[[Category: Scholl D]]
[[Category: Sigoillot M]]
[[Category: Steyaert J]]
[[Category: Urbatsch I]]