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3ch8

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Revision as of 06:14, 5 August 2016

The crystal structure of PDZ-Fibronectin fusion protein

Structural highlights

3ch8 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[LAP2_HUMAN] Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

We have established a new protein-engineering strategy termed "directed domain-interface evolution" that generates a binding site by linking two protein domains and then optimizing the interface between them. Using this strategy, we have generated synthetic two-domain "affinity clamps" using PDZ and fibronectin type III (FN3) domains as the building blocks. While these affinity clamps all had significantly higher affinity toward a target peptide than the underlying PDZ domain, two distinct types of affinity clamps were found in terms of target specificity. One type conserved the specificity of the parent PDZ domain, and the other increased the specificity dramatically. Here, we characterized their specificity profiles using peptide phage-display libraries and scanning mutagenesis, which suggested a significantly enlarged recognition site of the high-specificity affinity clamps. The crystal structure of a high-specificity affinity clamp showed extensive contacts with a portion of the peptide ligand that is not recognized by the parent PDZ domain, thus rationalizing the improvement of the specificity of the affinity clamp. A comparison with another affinity clamp structure showed that, although both had extensive contacts between PDZ and FN3 domains, they exhibited a large offset in the relative position of the two domains. Our results indicate that linked domains could rapidly fuse and evolve as a single functional module, and that the inherent plasticity of domain interfaces allows for the generation of diverse active-site topography. These attributes of directed domain-interface evolution provide facile means to generate synthetic proteins with a broad range of functions.

Structural basis for exquisite specificity of affinity clamps, synthetic binding proteins generated through directed domain-interface evolution.,Huang J, Makabe K, Biancalana M, Koide A, Koide S J Mol Biol. 2009 Oct 9;392(5):1221-31. Epub 2009 Jul 30. PMID:19646997^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Borg JP, Marchetto S, Le Bivic A, Ollendorff V, Jaulin-Bastard F, Saito H, Fournier E, Adelaide J, Margolis B, Birnbaum D. ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor. Nat Cell Biol. 2000 Jul;2(7):407-14. PMID:10878805 doi:10.1038/35017038
↑ Huang J, Makabe K, Biancalana M, Koide A, Koide S. Structural basis for exquisite specificity of affinity clamps, synthetic binding proteins generated through directed domain-interface evolution. J Mol Biol. 2009 Oct 9;392(5):1221-31. Epub 2009 Jul 30. PMID:19646997 doi:10.1016/j.jmb.2009.07.067

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ch8"

@@ Line 1: / Line 1: @@
 ==The crystal structure of PDZ-Fibronectin fusion protein==
 <StructureSection load='3ch8' size='340' side='right' caption='[[3ch8]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[3ch8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CH8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CH8 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ch8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ch8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ch8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ch8 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ch8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ch8 OCA], [http://pdbe.org/3ch8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ch8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ch8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ch8 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3ch8 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 26: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3ch8" style="background-color:#fffaf0;"></div>
 ==See Also==

3ch8

From Proteopedia

Revision as of 06:14, 5 August 2016

The crystal structure of PDZ-Fibronectin fusion protein

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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