PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Families in Gene Neighborhoods
June 2015
Expanding the Reach of SAD
April 2015
Greasing the Path for SFX
January 2015
Time-Resolved Crystallography with HATRX
December 2014
Structures Without Damage
August 2014
Error Prevention
July 2014
A Refined Refinement Strategy
May 2014
Membrane Proteome: Microcrystals Yield Big Data
April 2014
Optimizing Damage
February 2014
Getting Better at Low Resolution
January 2014
Building a Structural Library
November 2013
Drug Discovery: Identifying Dynamic Networks by CONTACT
October 2013
Microbiome: Solid-State NMR, Crystallized
September 2013
Fluorescence- and Chromatography-Based Protein Thermostability Assay
October 2012
Insert Here
October 2012
Native phasing
August 2012
Smaller may be better
April 2012
Metal mates
February 2012
Not so cool
December 2011
One from many
August 2011
Rosetta hone
July 2011
Solutions in the solution
June 2011
Beyond crystals, solutions, and powders
May 2011
Snapshot crystallography
March 2011
FERM-ly bound
February 2011
A new amphiphile for crystallizing membrane proteins
January 2011
'Super-resolution' large complexes
December 2010
Proteinase K and Digalacturonic Acid
September 2010
Some crystals like it hot
May 2010
Tips for crystallizing membrane proteins in lipidic mesophases
February 2010
Tackling the phase problem
November 2009
Crystallizing glycoproteins
September 2009
Crystals from recalcitrant proteins
August 2009
Tips for crystallizing membrane proteins
June 2009
Chaperone-assisted crystallography
March 2009
An “X-ray” ruler
January 2009
Methylation boosts protein crystallization
December 2008

Technology Topics Crystallography

FERM-ly bound

SBKB [doi:10.1038/sbkb.2011.04]
Technical Highlight - February 2011
Short description: X-ray crystallography of protein complex resolves a controversy regarding domain interactions.

The trilobed structure of DAL-1 (© Emw)

Tumor suppressors regulate a variety of processes in cells in order to restrain cancer progression and metastasis. The adhesion molecule tumor suppressor in lung cancer 1 (TSLC1) shows lost or diminished expression in many metastatic tumors. Through the 4.1 binding motif in its cytoplasmic tail (a hallmark of the protein 4.1 family), TSLC1 interacts with the FERM domain–containing tumor suppressor DAL-1, which controls cell adhesion. However, the significance and molecular details of this interaction are still not clear.

To examine this interaction, Hallberg and colleagues chose an X-ray crystallography approach and have uncovered the basis for the interaction between DAL-1 and TSLC1, providing the first crystal structure of 4.1 superfamily members in complex. The structure shows a peptide derived from TSLC1 binding in a conserved hydrophobic pocket in the C-lobe of the trilobed DAL-1 FERM domain. The overall structure of DAL-1 is not altered by the binding of TSLC1, but local conformational changes stabilize the interaction. These structural insights would be unavailable if either protein was studied individually, thus underscoring the utility of examining crystal structures of protein complexes.

Surface plasmon resonance analysis of TSLC1 binding to DAL-1 revealed both fast and slow reactions, likely representing initial binding and the resulting conformational changes, respectively. The TSLC1–DAL-1 structure has features similar to those due to interactions in other FERM domain–containing proteins and helps to resolve earlier controversy over domain interactions in 4.1 superfamily members. Although the full significance of interactions in FERM domain–containing proteins for tumor progression remains to be revealed, the model provided by this cocrystal will be integral to efforts to understand how tumor cells escape their local environment.

Steve Mason


  1. R.D. Busam et al. 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. Published online 3 December 2010. doi: 10.1074/jbc.M110.174011

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health