1i92
From Proteopedia
(New page: 200px<br /><applet load="1i92" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i92, resolution 1.70Å" /> '''STRUCTURAL BASIS OF ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1i92.gif|left|200px]]<br /><applet load="1i92" size=" | + | [[Image:1i92.gif|left|200px]]<br /><applet load="1i92" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1i92, resolution 1.70Å" /> | caption="1i92, resolution 1.70Å" /> | ||
'''STRUCTURAL BASIS OF THE NHERF PDZ1-CFTR INTERACTION'''<br /> | '''STRUCTURAL BASIS OF THE NHERF PDZ1-CFTR INTERACTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The PDZ1 domain of the Na(+)/H(+) exchanger regulatory factor (NHERF) | + | The PDZ1 domain of the Na(+)/H(+) exchanger regulatory factor (NHERF) binds with nanomolar affinity to the carboxyl-terminal sequence QDTRL of the cystic fibrosis transmembrane conductance regulator (CFTR) and plays a central role in the cellular localization and physiological regulation of this chloride channel. The crystal structure of human NHERF PDZ1 bound to the carboxyl-terminal peptide QDTRL has been determined at 1.7-A resolution. The structure reveals the specificity and affinity determinants of the PDZ1-CFTR interaction and provides insights into carboxyl-terminal leucine recognition by class I PDZ domains. The peptide ligand inserts into the PDZ1 binding pocket forming an additional antiparallel beta-strand to the PDZ1 beta-sheet, and an extensive network of hydrogen bonds and hydrophobic interactions stabilize the complex. Remarkably, the guanido group of arginine at position -1 of the CFTR peptide forms two salt bridges and two hydrogen bonds with PDZ1 residues Glu(43) and Asn(22), respectively, providing the structural basis for the contribution of the penultimate amino acid of the peptide ligand to the affinity of the interaction. |
==About this Structure== | ==About this Structure== | ||
| - | 1I92 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1I92 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I92 OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Karthikeyan, S.]] | [[Category: Karthikeyan, S.]] | ||
| - | [[Category: Ladias, J | + | [[Category: Ladias, J A.A.]] |
[[Category: Leung, T.]] | [[Category: Leung, T.]] | ||
[[Category: CL]] | [[Category: CL]] | ||
| Line 23: | Line 23: | ||
[[Category: pdz]] | [[Category: pdz]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:09:16 2008'' |
Revision as of 11:09, 21 February 2008
|
STRUCTURAL BASIS OF THE NHERF PDZ1-CFTR INTERACTION
Overview
The PDZ1 domain of the Na(+)/H(+) exchanger regulatory factor (NHERF) binds with nanomolar affinity to the carboxyl-terminal sequence QDTRL of the cystic fibrosis transmembrane conductance regulator (CFTR) and plays a central role in the cellular localization and physiological regulation of this chloride channel. The crystal structure of human NHERF PDZ1 bound to the carboxyl-terminal peptide QDTRL has been determined at 1.7-A resolution. The structure reveals the specificity and affinity determinants of the PDZ1-CFTR interaction and provides insights into carboxyl-terminal leucine recognition by class I PDZ domains. The peptide ligand inserts into the PDZ1 binding pocket forming an additional antiparallel beta-strand to the PDZ1 beta-sheet, and an extensive network of hydrogen bonds and hydrophobic interactions stabilize the complex. Remarkably, the guanido group of arginine at position -1 of the CFTR peptide forms two salt bridges and two hydrogen bonds with PDZ1 residues Glu(43) and Asn(22), respectively, providing the structural basis for the contribution of the penultimate amino acid of the peptide ligand to the affinity of the interaction.
About this Structure
1I92 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis of the Na+/H+ exchanger regulatory factor PDZ1 interaction with the carboxyl-terminal region of the cystic fibrosis transmembrane conductance regulator., Karthikeyan S, Leung T, Ladias JA, J Biol Chem. 2001 Jun 8;276(23):19683-6. Epub 2001 Apr 13. PMID:11304524
Page seeded by OCA on Thu Feb 21 13:09:16 2008
Categories: Homo sapiens | Single protein | Karthikeyan, S. | Ladias, J A.A. | Leung, T. | CL | Cftr | Complex | Crystal structure | Nherf | Pdz
