Document Detail

Principles for designing ideal protein structures.
MedLine Citation:
PMID:  23135467     Owner:  NLM     Status:  MEDLINE    
Unlike random heteropolymers, natural proteins fold into unique ordered structures. Understanding how these are encoded in amino-acid sequences is complicated by energetically unfavourable non-ideal features--for example kinked α-helices, bulged β-strands, strained loops and buried polar groups--that arise in proteins from evolutionary selection for biological function or from neutral drift. Here we describe an approach to designing ideal protein structures stabilized by completely consistent local and non-local interactions. The approach is based on a set of rules relating secondary structure patterns to protein tertiary motifs, which make possible the design of funnel-shaped protein folding energy landscapes leading into the target folded state. Guided by these rules, we designed sequences predicted to fold into ideal protein structures consisting of α-helices, β-strands and minimal loops. Designs for five different topologies were found to be monomeric and very stable and to adopt structures in solution nearly identical to the computational models. These results illuminate how the folding funnels of natural proteins arise and provide the foundation for engineering a new generation of functional proteins free from natural evolution.
Nobuyasu Koga; Rie Tatsumi-Koga; Gaohua Liu; Rong Xiao; Thomas B Acton; Gaetano T Montelione; David Baker
Related Documents :
23843247 - Community-wide evaluation of methods for predicting the effect of mutations on protein-...
23441177 - Identification of a novel protein-protein interaction motif mediating interaction of gp...
23918327 - Conjugation of nanoparticles to proteins.
23840197 - P-proteins in arabidopsis are heteromeric structures involved in rapid sieve tube sealing.
8686927 - Mass spectrometric determination of isotopic exchange rates of amide hydrogens located ...
21118957 - A constraint network of interactions: protein-protein interaction analysis of the yeast...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Nature     Volume:  491     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-08     Completed Date:  2013-01-10     Revised Date:  2013-07-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  222-7     Citation Subset:  IM    
University of Washington, Department of Biochemistry and Howard Hughes Medical Institute, Seattle, Washington 98195, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/2KL8;  2LN3;  2LTA;  2LV8;  2LVB
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Computer Simulation*
Models, Molecular*
Protein Folding*
Protein Stability*
Protein Structure, Secondary
Protein Structure, Tertiary
Proteins / chemistry*
Grant Support
U54 GM094597/GM/NIGMS NIH HHS; U54 GM094597/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Reg. No./Substance:
Comment In:
Nature. 2012 Nov 8;491(7423):204-5   [PMID:  23135466 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Switching the activity of a photoredox catalyst through reversible encapsulation and release.
Next Document:  Non-invasive imaging through opaque scattering layers.