Conversion of Monomeric Protein L to an Obligate Dimer by Computational Protein Design

Protein L consists of a single α-helix packed on a four-stranded β-sheet formed by two symmetrically opposed β-hairpins. We use a computer-based protein design procedure to stabilize a domain-swapped dimer of protein L in which the second β-turn straightens and the C-terminal strand inserts into the...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2001-09, Vol.98 (19), p.10687-10691
Main Authors: Kuhlman, Brian, O'Neill, Jason W., Kim, David E., Kam Y. J. Zhang, Baker, David
Format: Article
Language:English
Subjects:
Amino acids
Bacterial Proteins
Biochemistry
Biological Sciences
CAD
Computer aided design
Crystal structure
Crystallography
Dimerization
Dimers
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
Free energy
Guanidine
Models, Molecular
Molecules
Monomers
Mutagenesis
Mutation
Oligomers
Protein Denaturation
Protein Structure, Secondary
Proteins
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cited_by cdi_FETCH-LOGICAL-c555t-2b4d7f5cfdd1b082e37e24d73368fdb5fd3468a5c59a814afc879371bac36fbb3
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container_issue 19
container_start_page 10687
container_title Proceedings of the National Academy of Sciences - PNAS
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creator Kuhlman, Brian
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description Protein L consists of a single α-helix packed on a four-stranded β-sheet formed by two symmetrically opposed β-hairpins. We use a computer-based protein design procedure to stabilize a domain-swapped dimer of protein L in which the second β-turn straightens and the C-terminal strand inserts into the β-sheet of the partner. The designed obligate dimer contains three mutations (A52V, N53P, and G55A) and has a dissociation constant of ≈700 pM, which is comparable to the dissociation constant of many naturally occurring protein dimers. The structure of the dimer has been determined by x-ray crystallography and is close to the in silico model.
doi_str_mv 10.1073/pnas.181354398
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subjects Amino acids
Bacterial Proteins
Biochemistry
Biological Sciences
CAD
Computer aided design
Crystal structure
Crystallography
Dimerization
Dimers
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
Free energy
Guanidine
Models, Molecular
Molecules
Monomers
Mutagenesis
Mutation
Oligomers
Protein Denaturation
Protein Structure, Secondary
Proteins
title Conversion of Monomeric Protein L to an Obligate Dimer by Computational Protein Design
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