2h2c

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{{STRUCTURE_2h2c| PDB=2h2c | SCENE= }}
{{STRUCTURE_2h2c| PDB=2h2c | SCENE= }}
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'''Crystal Structure of ZO-1 PDZ1 Bound to a Phage-Derived Ligand (WRRTTWV)'''
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===Crystal Structure of ZO-1 PDZ1 Bound to a Phage-Derived Ligand (WRRTTWV)===
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==Overview==
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We report a structural comparison of the first PDZ domain of ZO-1 (ZO1-PDZ1) and the PDZ domain of Erbin (Erbin-PDZ). Although the binding profile of Erbin-PDZ is extremely specific ([D/E][T/S]WV(COOH)), that of ZO1-PDZ1 is similar ([R/K/S/T][T/S][W/Y][V/I/L](COOH)) but broadened by increased promiscuity for three of the last four ligand residues. Consequently, the biological function of ZO-1 is also broadened, as it interacts with both tight and adherens junction proteins, whereas Erbin is restricted to adherens junctions. Structural analyses reveal that the differences in specificity can be accounted for by two key differences in primary sequence. A reduction in the size of the hydrophobic residue at the base of the site(0) pocket enables ZO1-PDZ1 to accommodate larger C-terminal residues. A single additional difference alters the specificity of both site(-1) and site(-3). In ZO1-PDZ1, an Asp residue makes favorable interactions with both Tyr(-1) and Lys/Arg(-3). In contrast, Erbin-PDZ contains an Arg at the equivalent position, and this side chain cannot accommodate either Tyr(-1) or Lys/Arg(-3) but, instead, interacts favorably with Glu/Asp(-3). We propose a model for ligand recognition that accounts for interactions extending across the entire binding site but that highlights several key specificity switches within the PDZ domain fold.
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(as it appears on PubMed at http://www.pubmed.gov), where 16737969 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16737969}}
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
Comparative structural analysis of the Erbin PDZ domain and the first PDZ domain of ZO-1. Insights into determinants of PDZ domain specificity., Appleton BA, Zhang Y, Wu P, Yin JP, Hunziker W, Skelton NJ, Sidhu SS, Wiesmann C, J Biol Chem. 2006 Aug 4;281(31):22312-20. Epub 2006 May 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16737969 16737969]
Comparative structural analysis of the Erbin PDZ domain and the first PDZ domain of ZO-1. Insights into determinants of PDZ domain specificity., Appleton BA, Zhang Y, Wu P, Yin JP, Hunziker W, Skelton NJ, Sidhu SS, Wiesmann C, J Biol Chem. 2006 Aug 4;281(31):22312-20. Epub 2006 May 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16737969 16737969]
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Convergent and divergent ligand specificity among PDZ domains of the LAP and zonula occludens (ZO) families., Zhang Y, Yeh S, Appleton BA, Held HA, Kausalya PJ, Phua DC, Wong WL, Lasky LA, Wiesmann C, Hunziker W, Sidhu SS, J Biol Chem. 2006 Aug 4;281(31):22299-311. Epub 2006 May 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16737968 16737968]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Pdz domain]]
[[Category: Pdz domain]]
[[Category: Phage derived high affinity ligand]]
[[Category: Phage derived high affinity ligand]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:47:26 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 23:11:45 2008''

Revision as of 20:11, 28 July 2008

Image:2h2c.png

Template:STRUCTURE 2h2c

Crystal Structure of ZO-1 PDZ1 Bound to a Phage-Derived Ligand (WRRTTWV)

Template:ABSTRACT PUBMED 16737969

About this Structure

2H2C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Comparative structural analysis of the Erbin PDZ domain and the first PDZ domain of ZO-1. Insights into determinants of PDZ domain specificity., Appleton BA, Zhang Y, Wu P, Yin JP, Hunziker W, Skelton NJ, Sidhu SS, Wiesmann C, J Biol Chem. 2006 Aug 4;281(31):22312-20. Epub 2006 May 31. PMID:16737969

Convergent and divergent ligand specificity among PDZ domains of the LAP and zonula occludens (ZO) families., Zhang Y, Yeh S, Appleton BA, Held HA, Kausalya PJ, Phua DC, Wong WL, Lasky LA, Wiesmann C, Hunziker W, Sidhu SS, J Biol Chem. 2006 Aug 4;281(31):22299-311. Epub 2006 May 31. PMID:16737968

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