New conformational state of NHERF1-CXCR2 signaling complex captured by crystal lattice trapping

PloS One
Yuanyuan JiangZhe Yang

Abstract

NHERF1 is a PDZ adaptor protein that scaffolds the assembly of diverse signaling complexes and has been implicated in many cancers. However, little is known about the mechanism responsible for its scaffolding promiscuity or its ability to bind to multiple targets. Computational studies have indicated that PDZ promiscuity may be attributed to its conformational dynamics, but experimental evidence for this relationship remains very limited. Here we examine the conformational flexibility of the NHERF1 PDZ1 domain using crystal lattice trapping via solving PDZ1 structure of a new crystal form. The structure, together with prior PDZ1 structures of a different space group, reveals that 4 of 11 ligand-interacting residues undergo significant crystal packing-induced structural changes. Most of these residues correspond to the residues involved in allosteric transition when a peptide ligand binds. In addition, a subtle difference in ligand conformations causes the same peptide to bind in slightly different modes in different crystal forms. These findings indicate that substantial structural flexibility is present in the PDZ1 peptide-binding pocket, and the structural substate trapped in the present crystal form can be utilized to repres...Continue Reading

References

Feb 14, 1971·Journal of Molecular Biology·B Lee, F M Richards
Jul 21, 1995·Journal of Molecular Biology·X J ZhangB W Matthews
Jul 1, 1994·Protein Science : a Publication of the Protein Society·X J Zhang, B W Matthews
May 18, 1999·Acta Crystallographica. Section D, Biological Crystallography·E A Merritt
Oct 16, 1999·The Journal of Biological Chemistry·A RoujeinikovaD W Rice
Mar 30, 2000·Protein Science : a Publication of the Protein Society·D M van AaltenL Joshua-Tor
Jun 17, 2000·Trends in Cell Biology·C C GarnerR L Huganir
Sep 1, 2000·American Journal of Physiology. Renal Physiology·E J WeinmanS Shenolikar
Apr 3, 2001·Annual Review of Neuroscience·M Sheng, C Sala
Dec 31, 2003·Journal of Molecular Biology·Ernesto J FuentesAndrew L Lee
Apr 16, 2004·The Journal of Biological Chemistry·Thomas PöhlmannUlrike Alexiev
Nov 18, 2004·Physiology·Shirish ShenolikarEdward J Weinman
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Mar 3, 2005·Pflügers Archiv : European journal of physiology·Edward J WeinmanShirish Shenolikar
Nov 4, 2005·Nature·Elan Z EisenmesserDorothee Kern
Sep 28, 2006·Journal of the American Chemical Society·Nathalie BasdevantMarco Ceruso
Jul 21, 2007·Science·Michael A StifflerGavin MacBeath
Oct 27, 2007·Protein Science : a Publication of the Protein Society·Steven T RunyonSachdev S Sidhu
Feb 28, 2008·Current Opinion in Structural Biology·Maxim Totrov, Ruben Abagyan
Oct 3, 2008·PLoS Biology·Raffi TonikianSachdev S Sidhu
Dec 24, 2008·Journal of Bacteriology·Markus Liebscher, Anna Roujeinikova
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Oct 21, 2009·Nature Chemical Biology·David D BoehrPeter E Wright
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Mar 3, 2010·Protein Science : a Publication of the Protein Society·Z Nevin Gerek, S Banu Ozkan
Jun 1, 2010·Cell Communication and Signaling : CCS·Ho-Jin Lee, Jie J Zheng
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Aug 30, 2011·Pharmacological Reviews·Juan A Ardura, Peter A Friedman
Dec 29, 2011·The Journal of Biological Chemistry·Yanning WuChunying Li
Apr 13, 2012·Molecular Biology of the Cell·Rosa Angela CardoneStephan Joel Reshkin
Nov 8, 2012·PLoS Computational Biology·Márton MünzPhilip C Biggin
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Mar 20, 2014·Biochemical and Biophysical Research Communications·Yuanyuan JiangZhe Yang
Jan 28, 2020·American Journal of Physiology. Renal Physiology·Adrienne M Bushau-Sprinkle, Eleanor D Lederer
Sep 18, 2020·Antioxidants·Adrienne Bushau-SprinkleEleanor Lederer
Oct 24, 2020·International Journal of Molecular Sciences·Ananth Kumar KammalaRamkumar Menon

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Methods Mentioned

BETA
NMR
X-ray
PCR
size-exclusion chromatography

Software Mentioned

PHENIX
PHASER
PARVATI
AREAIMOL
PyMOL
COOT
HKL2000
ANISOANL
Molprobity

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