1ZDA

PHAGE-SELECTED MINI PROTEIN A DOMAIN, Z38, NMR, 24 STRUCTURES

Summary for 1ZDA

• Entry DOI: 10.2210/pdb1zda/pdb
• Descriptor: MINI PROTEIN A DOMAIN, Z38 (1 entity in total)
• Functional Keywords: igg binding domain, protein a mimic
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 4569.02

Authors

Starovasnik, M.A. (deposition date: 1997-07-09, release date: 1997-09-17, Last modification date: 2024-05-22)

Primary citation

Starovasnik, M.A.,Braisted, A.C.,Wells, J.A.
Structural mimicry of a native protein by a minimized binding domain.
Proc.Natl.Acad.Sci.USA, 94:10080-10085, 1997

PubMed Abstract: The affinity between molecules depends both on the nature and presentation of the contacts. Here, we observe coupling of functional and structural elements when a protein binding domain is evolved to a smaller functional mimic. Previously, a 38-residue form of the 59-residue B-domain of protein A, termed Z38, was selected by phage display. Z38 contains 13 mutations and binds IgG only 10-fold weaker than the native B-domain. We present the solution structure of Z38 and show that it adopts a tertiary structure remarkably similar to that observed for the first two helices of B-domain in the B-domain/Fc complex [Deisenhofer, J. (1981) Biochemistry 20, 2361-2370], although it is significantly less stable. Based on this structure, we have improved on Z38 by designing a 34-residue disulfide-bonded variant (Z34C) that has dramatically enhanced stability and binds IgG with 9-fold higher affinity. The improved stability of Z34C led to NMR spectra with much greater chemical shift dispersion, resulting in a more precisely determined structure. Z34C, like Z38, has a structure virtually identical to the equivalent region from native protein A domains. The well-defined hydrophobic core of Z34C reveals key structural features that have evolved in this small, functional domain. Thus, the stabilized two-helix peptide, about half the size and having one-third of the remaining residues altered, accurately mimics both the structure and function of the native domain.

PubMed: 9294166
DOI: 10.1073/pnas.94.19.10080

Experimental method

SOLUTION NMR