Relation of Mth to family B GPCRs and other Mth homologs.
(A) Phylogenetic relationship of transmembrane regions
of GPCR family B proteins. A phylogenetic tree was generated by using
the neighbor-joining method based on an alignment of transmembrane
domains generated with the clustalw program (25). The human
β-2 adrenergic receptor (not shown) served as the outgroup. A
subfamily consisting of ≈10 Mth-like proteins identified from the
Drosophila genome project clusters with Mth. CIRL,
calcium-independent receptor of α-latrotoxin; BAI-1, brain-specific
angiogenesis inhibitor 1; HE6, human epididymal gene product 6; SECR,
secretin receptor; VIPR, vasoactive intestinal peptide receptor; PTRR,
parathyroid hormone-related peptide receptor; GIPR, gastric inhibitory
peptide receptor; GLUCR, glucagon receptor; CALR, calcitonin receptor.
(B) Sequence alignment of the Mth ectodomain with
predicted homologs from the Drosophila genome. Residue
numbering begins at the first residue of the mature protein.
Crystallographically determined secondary-structural elements are shown
above the sequences. The 10 cysteines that form five disulfide bonds in
the Mth ectodomain are highlighted in yellow, and potential N-linked
glycosylation sites are highlighted in cyan.