Structural basis of tumor suppressor in lung cancer 1 (TSLC1) binding to differentially expressed in adenocarcinoma of the lung (DAL-1/4.1B)

J Biol Chem. 2011 Feb 11;286(6):4511-6. doi: 10.1074/jbc.M110.174011. Epub 2010 Dec 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / chemistry*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Crystallography, X-Ray
  • Humans
  • Immunoglobulins / chemistry*
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microfilament Proteins
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Surface Plasmon Resonance
  • Tumor Suppressor Proteins / chemistry*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism


  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • EPB41L3 protein, human
  • Immunoglobulins
  • Membrane Proteins
  • Microfilament Proteins
  • Tumor Suppressor Proteins

Associated data

  • PDB/2HE7
  • PDB/3BIN