2h2b: Difference between revisions
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'''Crystal Structure of ZO-1 PDZ1 Bound to a Phage-Derived Ligand (WRRTTYL)'''<br /> | '''Crystal Structure of ZO-1 PDZ1 Bound to a Phage-Derived Ligand (WRRTTYL)'''<br /> | ||
==Overview== | ==Overview== | ||
We report a structural comparison of the first PDZ domain of ZO-1 | 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. | ||
==About this Structure== | ==About this Structure== | ||
2H2B 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 ACY as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2H2B 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=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H2B OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Appleton, B | [[Category: Appleton, B A.]] | ||
[[Category: Hunziker, W.]] | [[Category: Hunziker, W.]] | ||
[[Category: Sidhu, S | [[Category: Sidhu, S S.]] | ||
[[Category: Skelton, N | [[Category: Skelton, N J.]] | ||
[[Category: Wiesmann, C.]] | [[Category: Wiesmann, C.]] | ||
[[Category: Wu, P.]] | [[Category: Wu, P.]] | ||
[[Category: Yin, J | [[Category: Yin, J P.]] | ||
[[Category: Zhang, Y.]] | [[Category: Zhang, Y.]] | ||
[[Category: ACY]] | [[Category: ACY]] | ||
| Line 26: | Line 25: | ||
[[Category: phage derived high affinity ligand]] | [[Category: phage derived high affinity ligand]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:37:28 2008'' | ||
Revision as of 18:37, 21 February 2008
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Crystal Structure of ZO-1 PDZ1 Bound to a Phage-Derived Ligand (WRRTTYL)
OverviewOverview
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.
About this StructureAbout this Structure
2H2B is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
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
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