4yl8
Crystal structure of the Crumbs/Moesin complexCrystal structure of the Crumbs/Moesin complex
Structural highlights
Function[MOES_MOUSE] Probably involved in connections of major cytoskeletal structures to the plasma membrane. [CRB_DROME] Plays a central role in cell polarity establishment. Participates in the assembly, positioning and maintenance of adherens junctions via its interaction with the SAC complex. Controls the coalescence of the spots of zonula adherens (ZA) into a adhesive ring around the cells. It may act as a signal. Involved in morphogenesis of the photoreceptor rhabdomere, for positioning and growth of rhabdomere and AJ during the crucial period of photoreceptor extension along the proximodistal axis of the retina.[1] Publication Abstract from PubMedThe type I transmembrane protein Crumbs (Crb) plays critical roles in the establishment and maintenance of cell polarities in diverse tissues. As such, mutations of Crb can cause different forms of cancers. The cell intrinsic role of Crb in cell polarity is governed by its conserved, 37-residue cytoplasmic tail (Crb-CT) via binding to Moesin and Protein associated with Lin7-1 (PALS1). However, the detailed mechanism governing the Crb/Moesin interaction and the balance of Crb in binding to Moesin and PALS1 are not well understood. Here we report the 1.5 A resolution crystal structure of the Moesin Protein 4.1/Ezrin/Radixin/Moesin (FERM) /Crb-CT complex, revealing that both the canonical FERM-binding motif and the Postsynaptic density protein-95/Disc large-1/ Zonula occludens-1 (PDZ)-binding motif of Crb contribute to the Crb/Moesin interaction. We further demonstrate that phosphorylation of Crb-CT by atypical protein kinase C (aPKC) disrupts the Crb/Moesin association, but has no impact on the Crb/PALS1 interaction. The above results indicate that, upon the establishment of the apical-basal polarity in epithelia, apical-localized aPKC can actively prevent the Crb/Moesin complex formation and thereby shift Crb to form complex with PALS1 at apical junctions. Therefore, Crb may serve as an aPKC-mediated sensor in coordinating contact-dependent cell growth inhibition in epithelial tissues. Structural basis for the phosphorylation-regulated interaction between the cytoplasmic tail of cell polarity protein Crumbs and the actin binding protein Moesin.,Wei Z, Li Y, Ye F, Zhang M J Biol Chem. 2015 Mar 19. pii: jbc.M115.643791. PMID:25792740[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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