This article is a U.S. Goverment work and, as such, is in the public domain in the United States of America.
1097-0134/asset/PROT_centre.gif?v=1&s=77b56b1f2cdaba74cb3bb149bd9b029cd8803cdb)
Research Article
Adaptations of the helix-grip fold for ligand binding and catalysis in the START domain superfamily †‡
Article first published online: 16 FEB 2001
DOI: 10.1002/1097-0134(20010501)43:2<134::AID-PROT1025>3.0.CO;2-I
Copyright © 2001 Wiley-Liss, Inc.
Issue
1097-0134/asset/cover.gif?v=1&s=d817e79b67ba6cacf8bdcce1a819c04de300a7e3 "Proteins: Structure, Function, and Bioinformatics")
Proteins: Structure, Function, and Bioinformatics
Volume 43, Issue 2, pages 134–144, 1 May 2001
Additional Information
How to Cite
Iyer, L. M., Koonin, E. V. and Aravind, L. (2001), Adaptations of the helix-grip fold for ligand binding and catalysis in the START domain superfamily . Proteins, 43: 134–144. doi: 10.1002/1097-0134(20010501)43:2<134::AID-PROT1025>3.0.CO;2-I
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A list of the Genbank identifier numbers of all the identified START domains, including the 59 plant proteins, is available at ftp://ncbi.nlm.nih.gov/pub/aravind/.
Publication History
- Issue published online: 16 FEB 2001
- Article first published online: 16 FEB 2001
- Manuscript Accepted: 14 DEC 2000
- Manuscript Received: 26 SEP 2000
- Abstract
- Article
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- Cited By
Keywords:
- START;
- aromatase;
- cyclase;
- lipid binding;
- birch allergen
Abstract
With a protein structure comparison, an iterative database search with sequence profiles, and a multiple-alignment analysis, we show that two domains with the helix-grip fold, the star-related lipid-transfer (START) domain of the MLN64 protein and the birch allergen, are homologous. They define a large, previously underappreciated superfamily that we call the START superfamily. In addition to the classical START domains that are primarily involved in eukaryotic signaling mediated by lipid binding and the birch antigen family that consists of plant proteins implicated in stress/pathogen response, the START superfamily includes bacterial polyketide cyclases/aromatases (e.g., TcmN and WhiE VI) and two families of previously uncharacterized proteins. The identification of this domain provides a structural prediction of an important class of enzymes involved in polyketide antibiotic synthesis and allows the prediction of their active site. It is predicted that all START domains contain a similar ligand-binding pocket. Modifications of this pocket determine the ligand-binding specificity and may also be the basis for at least two distinct enzymatic activities, those of a cyclase/aromatase and an RNase. Thus, the START domain superfamily is a rare case of the adaptation of a protein fold with a conserved ligand-binding mode for both a broad variety of catalytic activities and noncatalytic regulatory functions. Proteins 2001;43:134–144. © 2001 Wiley-Liss, Inc.