 GRAM Domain | |
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| Class:Phospholipid binding | |
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Structure:
 The structure of Gram domain from MTMR2 shows that the Gram sequence forms 5 β strands that are part of a larger motif that structurally adopt a PH domain fold. The Gram domain plus amino acid residues immediately following it form a tertiary structure consisting of a 7 stranded β sandwich with a α-helix at the C-terminal end. The structure of the Gram domain of MTMR2 is very similar to the pleckstrin PH domain. With the high conservation of residues that form the core of the domain, all predicted Gram domains would likely share the PH domain fold.
Structure Reference:
Begley, M.J. et al. (2003) Mol. Cell. 12(6): 1391-1402. PDB: 1LW3.
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Domain binding and function:
The GRAM (from glucosyltransferases, Rab-like GTPase activators and myotubularins) domain is approximately 70 amino acids in length consisting of a 7-stranded β sandwich with a α-helix at the C-terminal end. The MTMR2 GRAM domain showed an unexpectedly large fold similar to that of pleckstrin homology (PH) domain. GRAM domains are found in the myotubularin family of phosphatases and predicted to occur in ~180 proteins. Mutations have been identified in GRAM domains that lead to X-linked congenital myopathy, implicating its functional importance. Proteins that contain the GRAM domain appear to be predominately involved in membrane-coupled processes. Functional studies demonstrate that the GRAM domain is involved in PI-(3,5)P2 substrate recognition, PI-(3)-P/PI-(5)-P dependent oligomerization and PI-(5)-P specific allosteric activation of the myotubularin phosphatases.
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Examples of Proteins:
| GRAM domain protein |
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Specific Phosphoinositide ligands |
| MTMR2 |  |
PI-(3,5)-P2, PI-(5)-P
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| MTM1 , MTMR3, and MTMR6 | |
PI-(5)-P
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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