PDBsum entry 1zda

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Igg binding domain PDB id
Protein chain
38 a.a.
PDB id:
Name: Igg binding domain
Title: Phage-selected mini protein a domain, z38, nmr, 24 structures
Structure: Mini protein a domain, z38. Chain: a. Engineered: yes. Other_details: minimized, two-helix, igg-binding variant of protein a
Source: Synthetic construct. Organism_taxid: 32630
NMR struc: 24 models
Authors: M.A.Starovasnik
Key ref:
M.A.Starovasnik et al. (1997). Structural mimicry of a native protein by a minimized binding domain. Proc Natl Acad Sci U S A, 94, 10080-10085. PubMed id: 9294166 DOI: 10.1073/pnas.94.19.10080
09-Jul-97     Release date:   17-Sep-97    
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Protein chain
No UniProt id for this chain
Struc: 38 a.a.
Key:    Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     pathogenesis   1 term 
  Biochemical function     immunoglobulin binding     1 term  


DOI no: 10.1073/pnas.94.19.10080 Proc Natl Acad Sci U S A 94:10080-10085 (1997)
PubMed id: 9294166  
Structural mimicry of a native protein by a minimized binding domain.
M.A.Starovasnik, A.C.Braisted, J.A.Wells.
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.
  Selected figure(s)  
Figure 2.
Fig. 2. Overlay of the fingerprint region of COSY spectra for Z38 (black) and Z34C (red). Spectra were acquired under identical conditions at 8°C (pH 5.1). Selected crosspeaks are labeled for Z34C; arrows show the location of the same crosspeak in Z38. Complete 1H resonance assignments are available from the authors upon request.
Figure 4.
Fig. 4. NMR structure ensembles for (A) Z38 and (B) Z34C. In each case, 24 models are shown aligned using the backbone atoms of residues 10-36. Shown also are the coordinates for residues 7-38 from the^ crystal structure of the B-domain/Fc complex (red) (6). The^ disordered N-terminal residues 1-5 from Z38 are colored gray. Side chains from the hydrophobic core of Z34C are shown (Phe-6, Cys-10, Phe-14, Ala-17, Leu-18, Leu-23, Ile-32, Ile-35, and Cys-39). (C) The minimized mean structure of Z34C showing all side chains colored by amino acid type: hydrophobic (yellow), positively charged^ (blue), negatively charged (red), and polar (green); only those^ that are labeled are well defined in the NMR ensemble with 1^angular order parameters >0.9. Note that only the 1 = 60° orientation for Phe-14 is shown, but this side chain also exists in the 1^ = 180° conformation in solution. (D) Same as C, but rotated 90° with the Fc binding surface on top.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21360628 P.Järver, C.Mikaelsson, and A.E.Karlström (2011).
Chemical synthesis and evaluation of a backbone-cyclized minimized 2-helix Z-domain.
  J Pept Sci, 17, 463-469.  
21214700 S.K.Gidda, J.M.Shockey, M.Falcone, P.K.Kim, S.J.Rothstein, D.W.Andrews, J.M.Dyer, and R.T.Mullen (2011).
Hydrophobic-domain-dependent protein-protein interactions mediate the localization of GPAT enzymes to ER subdomains.
  Traffic, 12, 452-472.  
19422008 J.M.Webster, R.Zhang, S.S.Gambhir, Z.Cheng, and F.A.Syud (2009).
Engineered two-helix small proteins for molecular recognition.
  Chembiochem, 10, 1293-1296.  
19682997 S.Mukherjee, M.M.Waegele, P.Chowdhury, L.Guo, and F.Gai (2009).
Effect of macromolecular crowding on protein folding dynamics at the secondary structure level.
  J Mol Biol, 393, 227-236.  
18452237 H.Büning, L.Perabo, O.Coutelle, S.Quadt-Humme, and M.Hallek (2008).
Recent developments in adeno-associated virus vector technology.
  J Gene Med, 10, 717-733.  
18087661 H.Yanagida, T.Matsuura, and T.Yomo (2008).
Compensatory Evolution of a WW Domain Variant Lacking the Strictly Conserved Trp Residue.
  J Mol Evol, 66, 61-71.  
18606225 T.S.Raju (2008).
Terminal sugars of Fc glycans influence antibody effector functions of IgGs.
  Curr Opin Immunol, 20, 471-478.  
16939269 S.Boonyarattanakalin, S.E.Martin, Q.Sun, and B.R.Peterson (2006).
A synthetic mimic of human Fc receptors: defined chemical modification of cell surfaces enables efficient endocytic uptake of human immunoglobulin-G.
  J Am Chem Soc, 128, 11463-11470.  
16650069 H.Yang, P.V.Gurgel, and R.G.Carbonell (2005).
Hexamer peptide affinity resins that bind the Fc region of human immunoglobulin G.
  J Pept Res, 66, 120-137.  
15689399 R.K.Tabtiang, B.O.Cezairliyan, R.A.Grant, J.C.Cochrane, and R.T.Sauer (2005).
Consolidating critical binding determinants by noncyclic rearrangement of protein secondary structure.
  Proc Natl Acad Sci U S A, 102, 2305-2309.
PDB code: 1u9p
15551102 L.Di Costanzo, S.Geremia, L.Randaccio, F.Nastri, O.Maglio, A.Lombardi, and V.Pavone (2004).
Miniaturized heme proteins: crystal structure of Co(III)-mimochrome IV.
  J Biol Inorg Chem, 9, 1017-1027.
PDB code: 1pyz
  12646066 K.C.Hsiao, R.E.Brissette, P.Wang, P.W.Fletcher, V.Rodriguez, M.Lennick, A.J.Blume, and N.I.Goldstein (2003).
Peptides identify multiple hotspots within the ligand binding domain of the TNF receptor 2.
  Proteome Sci, 1, 1.  
12015147 B.K.Sharpe, J.M.Matthews, A.H.Kwan, A.Newton, D.A.Gell, M.Crossley, and J.P.Mackay (2002).
A new zinc binding fold underlines the versatility of zinc binding modules in protein evolution.
  Structure, 10, 639-648.
PDB code: 1liq
11782528 M.T.Pastor, M.López de la Paz, E.Lacroix, L.Serrano, and E.Pérez-Payá (2002).
Combinatorial approaches: a new tool to search for highly structured beta-hairpin peptides.
  Proc Natl Acad Sci U S A, 99, 614-619.
PDB codes: 1j4m 1k43
11932421 M.U.Ried, A.Girod, K.Leike, H.Büning, and M.Hallek (2002).
Adeno-associated virus capsids displaying immunoglobulin-binding domains permit antibody-mediated vector retargeting to specific cell surface receptors.
  J Virol, 76, 4559-4566.  
11266629 S.Gleiter, and H.Lilie (2001).
Coupling of antibodies via protein Z on modified polyoma virus-like particles.
  Protein Sci, 10, 434-444.  
10779412 A.G.Cochran (2000).
Antagonists of protein-protein interactions.
  Chem Biol, 7, R85-R94.  
10813830 A.Rajpal, and J.F.Kirsch (2000).
Role of the minor energetic determinants of chicken egg white lysozyme (HEWL) to the stability of the HEWL.antibody scFv-10 complex.
  Proteins, 40, 49-57.  
10618383 D.O.Alonso, and V.Daggett (2000).
Staphylococcal protein A: unfolding pathways, unfolded states, and differences between the B and E domains.
  Proc Natl Acad Sci U S A, 97, 133-138.  
10715107 D.Tolkatchev, A.Ng, W.Vranken, and F.Ni (2000).
Design and solution structure of a well-folded stack of two beta-hairpins based on the amino-terminal fragment of human granulin A.
  Biochemistry, 39, 2878-2886.
PDB code: 1g26
  10850804 P.Barthe, S.Rochette, C.Vita, and C.Roumestand (2000).
Synthesis and NMR solution structure of an alpha-helical hairpin stapled with two disulfide bridges.
  Protein Sci, 9, 942-955.
PDB code: 1ei0
10517154 B.Imperiali, and J.J.Ottesen (1999).
Uniquely folded mini-protein motifs.
  J Pept Res, 54, 177-184.  
  10422830 M.A.Starovasnik, M.P.O'Connell, W.J.Fairbrother, and R.F.Kelley (1999).
Antibody variable region binding by Staphylococcal protein A: thermodynamic analysis and location of the Fv binding site on E-domain.
  Protein Sci, 8, 1423-1431.  
10872466 W.F.DeGrado, C.M.Summa, V.Pavone, F.Nastri, and A.Lombardi (1999).
De novo design and structural characterization of proteins and metalloproteins.
  Annu Rev Biochem, 68, 779-819.  
9868362 G.Smith (1998).
Patch engineering: a general approach for creating proteins that have new binding activities.
  Trends Biochem Sci, 23, 457-460.  
9692327 G.Tuchscherer, L.Scheibler, P.Dumy, and M.Mutter (1998).
Protein design: on the threshold of functional properties.
  Biopolymers, 47, 63-73.  
9565750 J.P.Schneider, A.Lombardi, and W.F.DeGrado (1998).
Analysis and design of three-stranded coiled coils and three-helix bundles.
  Fold Des, 3, R29-R40.  
9565754 M.Struthers, J.J.Ottesen, and B.Imperiali (1998).
Design and NMR analyses of compact, independently folded BBA motifs.
  Fold Des, 3, 95.
PDB code: 1t8j
9294152 M.N.Nedwidek, and M.H.Hecht (1997).
Minimized protein structures: a little goes a long way.
  Proc Natl Acad Sci U S A, 94, 10010-10011.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.