Publication Date:
1998-12-16
Description:
Src homology 3 (SH3) and WW protein interaction domains bind specific proline-rich sequences. However, instead of recognizing critical prolines on the basis of side chain shape or rigidity, these domains broadly accepted amide N-substituted residues. Proline is apparently specifically selected in vivo, despite low complementarity, because it is the only endogenous N-substituted amino acid. This discriminatory mechanism explains how these domains achieve specific but low-affinity recognition, a property that is necessary for transient signaling interactions. The mechanism can be exploited: screening a series of ligands in which key prolines were replaced by nonnatural N-substituted residues yielded a ligand that selectively bound the Grb2 SH3 domain with 100 times greater affinity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nguyen, J T -- Turck, C W -- Cohen, F E -- Zuckermann, R N -- Lim, W A -- New York, N.Y. -- Science. 1998 Dec 11;282(5396):2088-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9851931" target="_blank"〉PubMed〈/a〉
Keywords:
*Adaptor Proteins, Signal Transducing
;
Amino Acid Sequence
;
Amino Acid Substitution
;
Animals
;
*Caenorhabditis elegans Proteins
;
Carrier Proteins/chemistry/metabolism
;
Crystallization
;
Crystallography, X-Ray
;
GRB2 Adaptor Protein
;
Helminth Proteins/chemistry/metabolism
;
Humans
;
Ligands
;
Models, Molecular
;
Molecular Sequence Data
;
Oligopeptides/chemistry/*metabolism
;
Phosphoproteins/chemistry/metabolism
;
Proline/chemistry/*metabolism
;
Protein Engineering
;
Proteins/chemistry/metabolism
;
Proto-Oncogene Proteins/chemistry/metabolism
;
Proto-Oncogene Proteins c-crk
;
Sequence Homology, Amino Acid
;
*src Homology Domains
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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