Crystal structure of the ectodomain of Methuselah, a Drosophila G protein-coupled receptor associated with extended lifespan.
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-A resolution crystal structure of the Mth extracellular region, revealing a folding topology in which three primarily beta-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.
West
A P
AP
Division of Biology 156-29, California Institute of Technology, Pasadena, CA 91125, USA.
Llamas
L L
LL
Snow
P M
PM
Benzer
S
S
Bjorkman
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004330:Drosophila / Q000737:chemistry*; D029721:Drosophila Proteins; D008017:Life Expectancy; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000145:classification; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000737:chemistry / Q000145:classification; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D008024:Ligands; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C115381:mth protein, Drosophila; C029937:secretin receptor