2GYT

Solution structure of the SAM (sterile alpha motif) domain of DLC1 (deleted in liver cancer 1)


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

The SAM domain of the RhoGAP DLC1 binds EF1A1 to regulate cell migration

Zhong, D.Zhang, J.Yang, S.Soh, U.J.K.Buschdorf, J.P.Zhou, Y.T.Yang, D.Low, B.C.

(2009) J Cell Sci 122: 414-424

  • DOI: https://doi.org/10.1242/jcs.027482
  • Primary Citation of Related Structures:  
    2GYT

  • PubMed Abstract: 

    Deleted in liver cancer 1 (DLC1) is a multi-modular Rho-GTPase-activating protein (RhoGAP) and a tumor suppressor. Besides its RhoGAP domain, functions of other domains in DLC1 remain largely unknown. By protein precipitation and mass spectrometry, we identified eukaryotic elongation factor 1A1 (EF1A1) as a novel partner for the sterile alpha motif (SAM) domain of DLC1 but not the SAM domain of DLC2. The solution structure of DLC1 SAM revealed a new monomeric fold with four parallel helices, similar to that of DLC2 SAM but distinct from other SAM domains. Mutating F38, L39 and F40 within a hydrophobic patch retained its overall structure but abolished its interaction with EF1A1 with F38 and L39 forming an indispensable interacting motif. DLC1 SAM did not localize to and was not required for DLC1 to suppress the turnover of focal adhesions. Instead, DLC1 SAM facilitated EF1A1 distribution to the membrane periphery and ruffles upon growth factor stimulation. Compared with wild-type DLC1, the non-interactive DLC1 mutant is less potent in suppressing cell migration, whereas overexpression of the DLC1 SAM domain alone, but not the non-interactive mutant SAM or DLC2 SAM, greatly enhanced cell migration. This finding reveals a novel contribution of the SAM-EF1A1 interaction as a potentially important GAP-independent modulation of cell migration by DLC1.


  • Organizational Affiliation

    Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, National University of Singapore, Singapore, Republic of Singapore.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Deleted in liver cancer 1 protein, isoform 276Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q96QB1 (Homo sapiens)
Explore Q96QB1 
Go to UniProtKB:  Q96QB1
PHAROS:  Q96QB1
GTEx:  ENSG00000164741 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ96QB1
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2007-04-24 
  • Deposition Author(s): Yang, S.

Revision History  (Full details and data files)

  • Version 1.0: 2007-04-24
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-03-09
    Changes: Data collection, Database references, Derived calculations
  • Version 1.4: 2024-05-29
    Changes: Data collection