Crystal structure of the ectodomain of Methuselah, a Drosophila G protein-coupled receptor associated with extended lifespan
Abstract
The Drosophila mutant methuselah (mth) was identified from a screen for single gene mutations that extended average lifespan. Mth mutants have a 35% increase in average lifespan and increased resistance to several forms of stress, including heat, starvation, and oxidative damage. The protein affected by this mutation is related to G protein-coupled receptors of the secretin receptor family. Mth, like secretin receptor family members, has a large N-terminal ectodomain, which may constitute the ligand binding site. Here we report the 2.3-Å resolution crystal structure of the Mth extracellular region, revealing a folding topology in which three primarily β-structure-containing domains meet to form a shallow interdomain groove containing a solvent-exposed tryptophan that may represent a ligand binding site. The Mth structure is analyzed in relation to predicted Mth homologs and potential ligand binding features.
Additional Information
© 2001 National Academy of Sciences. Contributed by Seymour Benzer, December 28, 2000. Published ahead of print March 13, 2001. We thank Yi-Jyun Lin and Laurent Seroude for helpful discussions, Duilio Cascio for assistance in MAD data collection, and members of the Bjorkman lab for critical reading of the manuscript. This work is supported by the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation, Grant DRG-1445 (A.P.W.), the Howard Hughes Medical Institute (P.J.B.), the Ellison Medical Foundation (S.B.), the National Science Foundation (S.B.), and the National Institutes of Health (S.B.). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.Attached Files
Published - PNAS-2001-West-3744-9.pdf
Supplemental Material - 6252fig4.pdf
Files
Name | Size | Download all |
---|---|---|
md5:cd8734d2b27f209af31c51753b7d8c6d
|
648.6 kB | Preview Download |
md5:afcf8b292fbb4f72146724d04acbd246
|
660.3 kB | Preview Download |
Additional details
- PMCID
- PMC31123
- Eprint ID
- 51971
- Resolver ID
- CaltechAUTHORS:20141119-131920312
- Damon Runyon-Walter Winchell Foundation Cancer Research Fund
- DRG-1445
- Howard Hughes Medical Institute (HHMI)
- Ellison Medical Foundation
- NSF
- NIH
- Created
-
2014-11-19Created from EPrint's datestamp field
- Updated
-
2021-11-10Created from EPrint's last_modified field