3bin
Structure of the DAL-1 and TSLC1 (372-383) complexStructure of the DAL-1 and TSLC1 (372-383) complex
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPerturbed cell-adhesion mechanisms are crucial for tumor invasion and metastasis. A cell-adhesion protein, Tumor Suppressor in Lung Cancer 1 (TSLC1), is inactivated in a majority of metastatic cancers. DAL-1 (differentially expressed in adenocarcinoma of the lung protein), another tumor suppressor, binds through its FERM domain to the TSLC1 C-terminal, 4.1 glycophorin C-like, cytoplasmic domain. However, the molecular basis for this interaction is unknown. Here, we describe the crystal structure of a complex between the DAL-1 FERM domain and a portion of the TSLC1 cytoplasmic domain. DAL-1 binds to TSLC1 through conserved residues in a well-defined hydrophobic pocket in the DAL-1 FERM domain's structural C-lobe. From the crystal structure, it is apparent that Tyr406 and Thr408 in the TSLC1 cytoplasmic domain form the most important interactions with DAL-1 and this was also confirmed by surface plasmon resonance studies. Our results refute earlier exon deletion experiments that indicated that glycophorin-C interacts with the alpha-lobe of 4.1 FERM domains. Structural basis of tumor suppressor in lung cancer 1 (TSLC1) binding to differentially expressed in adenocarcinoma of the lung (DAL-1/4.1B).,Busam RD, Thorsell AG, Flores A, Hammarstrom M, Persson C, Obrink B, Hallberg BM J Biol Chem. 2010 Dec 3. PMID:21131357[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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OCA- Homo sapiens
- Arrowsmith, C H.
- Berg, S Van Den.
- Berglund, H.
- Busam, R D.
- Collins, R.
- Dahlgren, L G.
- Edwards, A M.
- Flodin, S.
- Flores, A.
- Graslund, S.
- Hallberg, B M.
- Hammarstrom, M.
- Johansson, A.
- Johansson, I.
- Kallas, A.
- Karlberg, T.
- Kotenyova, T.
- Lehtio, L.
- Moche, M.
- Nilsson, M E.
- Nordlund, P.
- Nyman, T.
- Persson, C.
- Sagemark, J.
- Svensson, L.
- Thorsell, A G.
- Tresaugues, L.
- Weigelt, J.
- Welin, M.
- Actin-binding
- Anti-oncogene
- Apoptosis
- Cell adhesion
- Cell cycle
- Cytoskeleton
- Dal-1
- Developmental protein
- Differentiation
- Ferm domain
- Glycoprotein
- Immune response
- Immunoglobulin domain
- Membrane
- Phosphoprotein
- Spermatogenesis
- Structural protein
- Transmembrane
- Tslc1