1h0t: Difference between revisions

Revision as of 18:16, 2 May 2008

AN AFFIBODY IN COMPLEX WITH A TARGET PROTEIN: STRUCTURE AND COUPLED FOLDING

OverviewOverview

Combinatorial protein engineering provides powerful means for functional selection of novel binding proteins. One class of engineered binding proteins, denoted affibodies, is based on the three-helix scaffold of the Z domain derived from staphylococcal protein A. The Z(SPA-1) affibody has been selected from a phage-displayed library as a binder to protein A. Z(SPA-1) also binds with micromolar affinity to its own ancestor, the Z domain. We have characterized the Z(SPA-1) affibody in its uncomplexed state and determined the solution structure of a Z:Z(SPA-1) protein-protein complex. Uncomplexed Z(SPA-1) behaves as an aggregation-prone molten globule, but folding occurs on binding, and the original (Z) three-helix bundle scaffold is fully formed in the complex. The structural basis for selection and strong binding is a large interaction interface with tight steric and polar/nonpolar complementarity that directly involves 10 of 13 mutated amino acid residues on Z(SPA-1). We also note similarities in how the surface of the Z domain responds by induced fit to binding of Z(SPA-1) and Ig Fc, respectively, suggesting that the Z(SPA-1) affibody is capable of mimicking the morphology of the natural binding partner for the Z domain.

About this StructureAbout this Structure

1H0T is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.

ReferenceReference

An affibody in complex with a target protein: structure and coupled folding., Wahlberg E, Lendel C, Helgstrand M, Allard P, Dincbas-Renqvist V, Hedqvist A, Berglund H, Nygren PA, Hard T, Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3185-90. Epub 2003 Feb 19. PMID:12594333 Page seeded by OCA on Fri May 2 18:16:16 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:1h0t.jpg|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_1h0t", creates the "Structure Box" on the page.
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+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h0t OCA], [http://www.ebi.ac.uk/pdbsum/1h0t PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1h0t RCSB]</span>
-}}
 '''AN AFFIBODY IN COMPLEX WITH A TARGET PROTEIN: STRUCTURE AND COUPLED FOLDING'''
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 [[Category: Nygren, P A.]]
 [[Category: Wahlberg, E.]]
-[[Category: affibody]]
+[[Category: Affibody]]
-[[Category: coupled protein folding]]
+[[Category: Coupled protein folding]]
-[[Category: igg binding protein some]]
+[[Category: Igg binding protein some]]
-[[Category: induced fit]]
+[[Category: Induced fit]]
-[[Category: molecular recognition]]
+[[Category: Molecular recognition]]
-[[Category: molten globule]]
+[[Category: Molten globule]]
-[[Category: nmr spectroscopy]]
+[[Category: Nmr spectroscopy]]
-[[Category: protein engineering]]
+[[Category: Protein engineering]]
-[[Category: protein-protein interaction]]
+[[Category: Protein-protein interaction]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 18:16:16 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:55:20 2008''