The L3 loop: A structural motif determining specific interactions between SMAD proteins and TGF-β receptors Journal Article
| Authors: | Lo, R. S.; Chen, Y. G.; Shi, Y.; Pavletich, N. P.; Massagué, J. |
| Article Title: | The L3 loop: A structural motif determining specific interactions between SMAD proteins and TGF-β receptors |
| Abstract: | Signal transduction specificity in the transforming growth factor-β (TGF-β) system is determined by ligand activation of a receptor complex which then recruits and phosphorylates a subset of SMAD proteins including Smads 1 and 2. These then associate with Smad4 and move into the nucleus where they regulate transcription. We have identified a discrete surface structure in Smads 1 and 2 that mediates and specifies their receptor interactions. This structure is the L3 loop, a 17 amino acid region that protrudes from the core of the conserved SMAD C-terminal domain. The L3 loop sequence is invariant among TGF-β- and bone morphogenetic protein (BMP)-activated SMADS, but differs at two positions between these two groups. Swapping these two amino acids in Smads 1 and 2 induces a gain or loss, respectively, in their ability to associate with the TGF-β receptor complex and causes a switch in the phosphorylation of Smads 1 and 2 by the BMP and TGF-β receptors, respectively. A full switch in phosphorylation and activation of Smads 1 and 2 is obtained by swapping both these two amino acids and four amino acids near the C-terminal receptor phosphorylation sites. These studies identify the L3 loop as a determinant of specific SMAD-receptor interactions, and indicate that the L3 loop, together with the C-terminal tail, specifies SMAD activation. |
| Keywords: | signal transduction; controlled study; dna-binding proteins; nonhuman; animal cell; bone morphogenetic protein; smad2 protein; transforming growth factor beta; carboxy terminal sequence; structure-activity relationship; phosphorylation; animalia; transcription regulation; amino acid sequence; molecular sequence data; receptors, transforming growth factor beta; smad proteins; models, molecular; protein structure, tertiary; trans-activators; protein secondary structure; repressor proteins; transforming growth factor-β; basic helix-loop-helix leucine zipper transcription factors; growth factor receptor; receptor interactions; humans; human; priority journal; article; l3 loop |
| Journal Title: | EMBO Journal |
| Volume: | 17 |
| Issue: | 4 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 1998-02-15 |
| Start Page: | 996 |
| End Page: | 1005 |
| Language: | English |
| DOI: | 10.1093/emboj/17.4.996 |
| PUBMED: | 9463378 |
| PROVIDER: | scopus |
| PMCID: | PMC1170449 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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