1zda
From Proteopedia
(New page: 200px<br /><applet load="1zda" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zda" /> '''PHAGE-SELECTED MINI PROTEIN A DOMAIN, Z38, N...) |
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| - | [[Image:1zda.jpg|left|200px]]<br /><applet load="1zda" size=" | + | [[Image:1zda.jpg|left|200px]]<br /><applet load="1zda" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1zda" /> | caption="1zda" /> | ||
'''PHAGE-SELECTED MINI PROTEIN A DOMAIN, Z38, NMR, 24 STRUCTURES'''<br /> | '''PHAGE-SELECTED MINI PROTEIN A DOMAIN, Z38, NMR, 24 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The affinity between molecules depends both on the nature and presentation | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZDA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http:// | + | 1ZDA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZDA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Synthetic construct]] | [[Category: Synthetic construct]] | ||
| - | [[Category: Starovasnik, M | + | [[Category: Starovasnik, M A.]] |
[[Category: igg binding domain]] | [[Category: igg binding domain]] | ||
[[Category: protein a mimic]] | [[Category: protein a mimic]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:14:26 2008'' |
Revision as of 14:14, 21 February 2008
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PHAGE-SELECTED MINI PROTEIN A DOMAIN, Z38, NMR, 24 STRUCTURES
Overview
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.
About this Structure
1ZDA is a Protein complex structure of sequences from Synthetic construct. Full crystallographic information is available from OCA.
Reference
Structural mimicry of a native protein by a minimized binding domain., Starovasnik MA, Braisted AC, Wells JA, Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10080-5. PMID:9294166
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