1h4r
From Proteopedia
Crystal Structure of the FERM domain of Merlin, the Neurofibromatosis 2 Tumor Suppressor Protein.
Structural highlights
DiseaseMERL_HUMAN Neurofibromatosis type 3;Neurofibromatosis type 2. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry. FunctionMERL_HUMAN Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNeurofibromatosis type 2 is an autosomal dominant disorder characterized by central nervous system tumors. The cause of the disease has been traced to mutations in the gene coding for a protein that is alternately called merlin or schwannomin and is a member of the ERM family (ezrin, radixin and moesin). The ERM proteins link the cytoskeleton to the cell membrane either directly through integral membrane proteins or indirectly through membrane-associated proteins. In this paper, the expression, purification, crystallization and crystal structure of the N-terminal domain of merlin are described. The crystals exhibit the symmetry of space group P2(1)2(1)2(1), with two molecules in the asymmetric unit. The recorded diffraction pattern extends to 1.8A resolution. The structure was solved by the molecular-replacement method and the model was refined to a conventional R value of 19.3% (R(free) = 22.7%). The N-terminal domain of merlin closely resembles those described for the corresponding domains in moesin and radixin and exhibits a cloverleaf architecture with three distinct subdomains. The structure allows a better rationalization of the impact of selected disease-causing mutations on the integrity of the protein. The structure of the FERM domain of merlin, the neurofibromatosis type 2 gene product.,Kang BS, Cooper DR, Devedjiev Y, Derewenda U, Derewenda ZS Acta Crystallogr D Biol Crystallogr. 2002 Mar;58(Pt 3):381-91. Epub 2002, Feb 21. PMID:11856822[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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