2b87
Structural basis for molecular recognition in an affibody:affibody complex
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OverviewOverview
Affibody molecules constitute a class of engineered binding proteins based, on the 58-residue three-helix bundle Z domain derived from staphylococcal, protein A (SPA). Affibody proteins are selected as binders to target, proteins by phage display of combinatorial libraries in which typically 13, side-chains on the surface of helices 1 and 2 in the Z domain have been, randomized. The Z(Taq):anti-Z(Taq) affibody-affibody complex, consisting, of Z(Taq), originally selected as a binder to Taq DNA polymerase, and, anti-Z(Taq), selected as binder to Z(Taq), is formed with a dissociation, constant K(d) approximately 100 nM. We have determined high-precision, solution structures of free Z(Taq) and anti-Z(Taq), and the, Z(Taq):anti-Z(Taq) complex under identical experimental conditions (25, degrees C in 50 mM NaCl with 20 mM potassium phosphate buffer at pH 6.4)., The complex is formed with helices 1 and 2 of anti-Z(Taq) in perpendicular, contact with helices 1 and 2 of Z(Taq). The interaction surface is large (, approximately 1670 A(2)) and unusually non-polar (70 %) compared to other, protein-protein complexes. It involves all varied residues on anti-Z(Taq), most corresponding (Taq DNA polymerase binding) side-chains on Z(Taq), and, several additional side-chain and backbone contacts. Other notable, features include a substantial rearrangement (induced fit) of aromatic, side-chains in Z(Taq) upon binding, a close contact between glycine, residues in the two subunits that might involve aliphatic glycine Halpha, to backbone carbonyl hydrogen bonds, and four hydrogen bonds made by the, two guanidinium N(eta)H(2) groups of an arginine side-chain. Comparisons, of the present structure with other data for affibody proteins and the Z, domain suggest that intrinsic binding properties of the originating SPA, surface might be inherited by the affibody binders. A thermodynamic, characterization of Z(Taq) and anti-Z(Taq) is presented in an accompanying, paper.
About this StructureAbout this Structure
2B87 is a Protein complex structure of sequences from Staphylococcus aureus. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for molecular recognition in an affibody:affibody complex., Lendel C, Dogan J, Hard T, J Mol Biol. 2006 Jun 23;359(5):1293-304. Epub 2006 May 6. PMID:16750222
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