Document Detail


Principles for designing ideal protein structures.
MedLine Citation:
PMID:  23135467     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Nobuyasu Koga; Rie Tatsumi-Koga; Gaohua Liu; Rong Xiao; Thomas B Acton; Gaetano T Montelione; David Baker
Related Documents :
23132507 - Protein metalation by metal-based drugs: reactions of cytotoxic gold compounds with cyt...
23103507 - A lipid-dependent link between activity and oligomerization state of the m. tuberculosi...
23692917 - Molecularly imprinted polydopamine nano-layer on the pore surface of porous particles f...
24330657 - Temperature-regulated expression of outer membrane proteins in shigella flexneri.
17218337 - Bacteriophage mu c protein is a new member of unusual leucine zipper-hth class of prote...
15609697 - Mediastinal pancreatic pseudocyst caused by obstruction of the pancreatic duct was elim...
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    
Affiliation:
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
Descriptor/Qualifier:
Computer Simulation*
Models, Molecular*
Protein Folding*
Protein Stability*
Protein Structure, Secondary
Protein Structure, Tertiary
Proteins / chemistry*
Thermodynamics
Grant Support
ID/Acronym/Agency:
U54 GM094597/GM/NIGMS NIH HHS; U54 GM094597/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Proteins
Comments/Corrections
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.