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Crystal structure of the ectodomain of Methuselah, a Drosophila G protein-coupled receptor associated with extended lifespan

West, Anthony P., Jr. and Llamas, Lynda L. and Snow, Peter M. and Benzer, Seymour and Bjorkman, Pamela J. (2001) Crystal structure of the ectodomain of Methuselah, a Drosophila G protein-coupled receptor associated with extended lifespan. Proceedings of the National Academy of Sciences of the United States of America, 98 (7). pp. 3744-3749. ISSN 0027-8424. PMCID PMC31123. https://resolver.caltech.edu/CaltechAUTHORS:20141119-131920312

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.051625298DOIArticle
http://www.pnas.org/content/98/7/3744PublisherArticle
http://www.pnas.org/content/suppl/2001/03/08/051625298.DC1/6252Fig4Legend.htmlPublisherSupplemental Figure
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC31123/PubMed CentralArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
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.
Funders:
Funding AgencyGrant Number
Damon Runyon-Walter Winchell Foundation Cancer Research FundDRG-1445
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Ellison Medical FoundationUNSPECIFIED
NSFUNSPECIFIED
NIHUNSPECIFIED
Issue or Number:7
PubMed Central ID:PMC31123
Record Number:CaltechAUTHORS:20141119-131920312
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141119-131920312
Official Citation:West, A. P., Llamas, L. L., Snow, P. M., Benzer, S., & Bjorkman, P. J. (2001). Crystal structure of the ectodomain of Methuselah, a Drosophila G protein-coupled receptor associated with extended lifespan. Proceedings of the National Academy of Sciences, 98(7), 3744-3749. doi: 10.1073/pnas.051625298
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51971
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:19 Nov 2014 23:12
Last Modified:03 Oct 2019 07:38

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