1sgh
From Proteopedia
Moesin FERM domain bound to EBP50 C-terminal peptide
Structural highlights
Disease[NHRF1_HUMAN] Defects in SLC9A3R1 are the cause of hypophosphatemic nephrolithiasis/osteoporosis type 2 (NPHLOP2) [MIM:612287]. Hypophosphatemia results from idiopathic renal phosphate loss. It contributes to the pathogenesis of hypophosphatemic urolithiasis (formation of urinary calculi) as well to that of hypophosphatemic osteoporosis (bone demineralization).[1] [2] Function[MOES_HUMAN] Probably involved in connections of major cytoskeletal structures to the plasma membrane. May inhibit herpes simplex virus 1 infection at an early stage.[3] [NHRF1_HUMAN] Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules.[4] [5] [6] [7] 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 PubMedMembers of the ezrin-radixin-moesin (ERM) protein family serve as regulated microfilament-membrane crosslinking proteins that, upon activation, bind the scaffolding protein ERM-phosphoprotein of 50 kDa (EBP50). Here we report a 3.5 A resolution diffraction analysis of a complex between the active moesin N-terminal FERM domain and a 38 residue peptide from the C terminus of EBP50. This crystallographic result, combined with sequence and structural comparisons, suggests that the C-terminal 11 residues of EBP50 binds as an alpha-helix at the same site occupied in the dormant monomer by the last 11 residues of the inhibitory moesin C-terminal tail. Biochemical support for this interpretation derives from in vitro studies showing that appropriate mutations in both the EBP50 tail peptide and the FERM domain reduce binding, and that a peptide representing just the C-terminal 14 residues of EBP50 also binds to moesin. Combined with the recent identification of the I-CAM-2 binding site on the ERM FERM domain (Hamada, K., Shimizu, T., Yonemura, S., Tsukita, S., and Hakoshima, T. (2003) EMBO J. 22, 502-514), this study reveals that the FERM domain contains two distinct binding sites for membrane-associated proteins. The contribution of each ligand to ERM function can now be dissected by making structure-based mutations that specifically affect the binding of each ligand. The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain.,Finnerty CM, Chambers D, Ingraffea J, Faber HR, Karplus PA, Bretscher A J Cell Sci. 2004 Mar 15;117(Pt 8):1547-52. PMID:15020681[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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