Consolidating Critical Binding Determinants by Noncyclic Rearrangement of Protein Secondary Structure

We designed a single-chain variant of the Arc repressor homodimer in which the β strands that contact operator DNA are connected by a hairpin turn and the α helices that form the tetrahelical scaffold of the dimer are attached by a short linker. The designed protein represents a noncyclic permutatio...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2005-02, Vol.102 (7), p.2305-2309
Hauptverfasser: Tabtiang, Ramon K., Cezairliyan, Brent O., Grant, Robert A., Cochrane, Jesse C., Sauer, Robert T.
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container_end_page 2309
container_issue 7
container_start_page 2305
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 102
creator Tabtiang, Ramon K.
Cezairliyan, Brent O.
Grant, Robert A.
Cochrane, Jesse C.
Sauer, Robert T.
description We designed a single-chain variant of the Arc repressor homodimer in which the β strands that contact operator DNA are connected by a hairpin turn and the α helices that form the tetrahelical scaffold of the dimer are attached by a short linker. The designed protein represents a noncyclic permutation of secondary structural elements in another single-chain Arc molecule (Arc-L1-Arc), in which the two subunits are fused by a single linker. The permuted protein binds operator DNA with nanomolar affinity, refolds on the submillisecond time scale, and is as stable as Arc-L1-Arc. The crystal structure of the permuted protein reveals an essentially wild-type fold, demonstrating that crucial folding information is not encoded in the wild-type order of secondary structure. Noncyclic rearrangement of secondary structure may allow grouping of critical activesite residues in other proteins and could be a useful tool for protein design and minimization.
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subjects Bacteriophage P22 - chemistry
Bacteriophage P22 - genetics
Biochemistry
Biological Sciences
Crystal structure
Crystallography, X-Ray
Crystals
Datasets
Deoxyribonucleic acid
Dimers
DNA
DNA, Viral - genetics
DNA, Viral - metabolism
Kinetics
Models, Molecular
Molecules
Protein Binding
Protein Folding
Protein refolding
Protein Structure, Secondary
Proteins
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Repressor Proteins - chemistry
Repressor Proteins - genetics
Repressor Proteins - metabolism
Structural members
Viral Proteins - chemistry
Viral Proteins - genetics
Viral Proteins - metabolism
Viral Regulatory and Accessory Proteins
title Consolidating Critical Binding Determinants by Noncyclic Rearrangement of Protein Secondary Structure
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