Structural highlights
Function[LIN12_CAEEL] Involved in several cell fate decisions that require cell-cell interactions. It is possible that lin-12 encodes a membrane-bound receptor for a signal that enables expression of the ventral uterine precursor cell fate. Activity in cell fate decisions and tumorigenesis is negatively regulated by sel-10.[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 PubMedThe Notch pathway is a conserved cell-to-cell signaling mechanism, in which extracellular signals are transduced into transcriptional outputs through the nuclear effector CSL. CSL is converted from a repressor to an activator through the formation of the CSL-NotchIC-Mastermind ternary complex. The RAM (RBP-J associated molecule) domain of NotchIC avidly interacts with CSL; however, its role in assembly of the CSL-NotchIC-Mastermind ternary complex is not understood. Here we provide a comprehensive thermodynamic, structural, and biochemical analysis of the RAM-CSL interaction for components from both mouse and worm. Our binding data show that RAM and CSL form a high affinity complex in the presence or absence of DNA. Our structural studies reveal a striking distal conformational change in CSL upon RAM binding, which creates a docking site for Mastermind to bind to the complex. Finally, we show that the addition of a RAM peptide in trans facilitates formation of the CSL-NotchIC-Mastermind ternary complex in vitro. RAM-induced allostery facilitates assembly of a notch pathway active transcription complex.,Friedmann DR, Wilson JJ, Kovall RA J Biol Chem. 2008 May 23;283(21):14781-91. Epub 2008 Apr 1. PMID:18381292[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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