title: Structure of the N-terminal domain of the protein Expansion: an 'Expansion' to the Smad MH2 fold.
abstract: Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF-β signalling pathway. Apart from Smads and Expansion, no other type of protein belonging to the known kingdoms of life contains MH2 domains. To compare the Expansion and Smad MH2 domains, the crystal structure of the Expansion domain was determined at 1.6 Å resolution, the first structure of a non-Smad MH2 domain to be characterized to date. The structure displays the main features of the canonical MH2 fold with two main differences: the addition of an α-helical region and the remodelling of a protein-interaction site that is conserved in the MH2 domain of Smads. Owing to these differences, to the new domain was referred to as Nα-MH2. Despite the presence of the Nα-MH2 domain, Expansion does not participate in TGF-β signalling; instead, it is required for other activities specific to the protostome phyla. Based on the structural similarities to the MH2 fold, it is proposed that the Nα-MH2 domain should be classified as a new member of the Smad/FHA superfamily.
authors: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain.
authors: Mads
authors: M
authors: Beich-Frandsen
authors: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain.
authors: Eric
authors: E
authors: Aragón
authors: Institut de Biologia Molecular de Barcelona, IBMB-CSIC, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors: Marta
authors: M
authors: Llimargas
authors: ALBA Synchrotron, BP 1413, km 3.3, Cerdanyola del Vallès, Spain.
authors: Jordi
authors: J
authors: Benach
authors: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain.
authors: Antoni
authors: A
authors: Riera
authors: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain.
authors: Joan
authors: J
authors: Pous
authors: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain.
authors: Maria J
authors: MJ
authors: Macias
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004330:Drosophila / Q000737:chemistry* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D060066:Protein Interaction Maps; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction; D051785:Smad Proteins / Q000737:chemistry* / Q000378:metabolism; D051899:Smad2 Protein / Q000737:chemistry* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D051785:Smad Proteins; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C000592845:exp protein, Drosophila
keywords: Expansion protein; MH2 domain; Smad homology domain 2; Smad/FHA protein superfamily; phenix.mr_rosetta; protein–protein interaction