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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilungsunabhängige Arbeitsgruppen     Display Documents

ID: 733159.0, MPI für Entwicklungsbiologie / Abteilungsunabhängige Arbeitsgruppen
De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy
Authors:Huang, P. S.; Feldmeier, K.; Parmeggiani, F.; Fernandez Velasco, D. A.; Hocker, B.; Baker, D.
Date of Publication (YYYY-MM-DD):2016-01
Title of Journal:Nat Chem Biol
Issue / Number:1
Start Page:29
End Page:34
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the TIM-barrel fold. Here we describe the computational design of four-fold symmetrical (beta/alpha)8 barrels guided by geometrical and chemical principles. Experimental characterization of 33 designs revealed the importance of side chain-backbone hydrogen bonds for defining the strand register between repeat units. The X-ray crystal structure of a designed thermostable 184-residue protein is nearly identical to that of the designed TIM-barrel model. PSI-BLAST searches do not identify sequence similarities to known TIM-barrel proteins, and sensitive profile-profile searches indicate that the design sequence is distant from other naturally occurring TIM-barrel superfamilies, suggesting that Nature has sampled only a subset of the sequence space available to the TIM-barrel fold. The ability to design TIM barrels de novo opens new possibilities for custom-made enzymes.
Free Keywords:Circular Dichroism; Crystallography, X-Ray; Hydrogen Bonding; *Models, Molecular; Protein Conformation; Protein Engineering/*methods; *Protein Folding; Proteins/chemical synthesis/*chemistry
External Publication Status:published
Document Type:Article
Affiliations:MPI für Entwicklungsbiologie/Abteilungsunabhängige Arbeitsgruppen/Arbeitsgruppe Höcker
External Affiliations:Institute for Protein Design, University of Washington, Seattle, Washington, USA. Max Planck Institute for Developmental Biology, Tubingen, Germany. Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Ciudad Universitaria, Mexico DF, Mexico. Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
Identifiers:ISSN:1552-4469 (Electronic) 1552-4450 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/26595462 [ID No:2]
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