title: The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization.
abstract: The sterile alpha motif (SAM) domain is a novel protein module of approximately 70 amino acids that is found in a variety of signaling molecules including tyrosine and serine/threonine protein kinases, cytoplasmic scaffolding and adaptor proteins, regulators of lipid metabolism, and GTPases as well as members of the ETS family of transcription factors. The SAM domain can potentially function as a protein interaction module through the ability to homo- and hetero-oligomerize with other SAM domains. This functional property elicits the oncogenic activation of chimeric proteins arising from translocation of the SAM domain of TEL to coding regions of the betaPDGF receptor, Abl, JAK2 protein kinase and the AML1 transcription factor. Here we describe the 2.0 A X-ray crystal structure of a SAM domain homodimer from the intracellular region of the EphA4 receptor tyrosine kinase. The structure reveals a mode of dimerization that we predict is shared amongst the SAM domains of the Eph receptor tyrosine kinases and possibly other SAM domain containing proteins. These data indicate a mechanism through which an independently folding protein module can form homophilic complexes that regulate signaling events at the membrane and in the nucleus.
authors.affiliation: Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Stapleton
authors.forename: I
authors.initials: I
authors.lastname: Balan
authors.forename: T
authors.initials: T
authors.lastname: Pawson
authors.forename: F
authors.initials: F
authors.lastname: Sicheri
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D020794:Receptor Protein-Tyrosine Kinases