1. Structural Basis of Tumor Suppressor in Lung Cancer 1 (TSLC1) Binding to Differentially Expressed in Adenocarcinoma of the Lung (DAL-1/4.1B)*
- Author
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Björn Öbrink, Camilla Persson, Ann-Gerd Thorsell, A. Flores, Robert D. Busam, Martin Hammarström, and B. Martin Hallberg
- Subjects
Immunoglobulins ,Plasma protein binding ,Biology ,Crystallography, X-Ray ,Biochemistry ,Structure-Activity Relationship ,Protein structure ,Adenocarcinoma of the lung ,medicine ,Glycophorin ,Humans ,Cell adhesion ,Protein Structure, Quaternary ,Molecular Biology ,FERM domain ,Cell adhesion molecule ,Tumor Suppressor Proteins ,Microfilament Proteins ,Cell Adhesion Molecule-1 ,Membrane Proteins ,Cell Biology ,Glycophorin C ,Surface Plasmon Resonance ,medicine.disease ,Molecular biology ,Cell biology ,Protein Structure, Tertiary ,Protein Structure and Folding ,biology.protein ,Cell Adhesion Molecules ,Protein Binding - Abstract
Perturbed cell adhesion mechanisms are crucial for tumor invasion and metastasis. A cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1), 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 structural C-lobe of the DAL-1 FERM domain. From the crystal structure, it is apparent that Tyr(406) and Thr(408) 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 α-lobe of 4.1 FERM domains.
- Published
- 2010