The molecular mechanism of notch activation

Klaus N. Lovendahl, Stephen C. Blacklow, Wendy R. Gordon

Research output: Chapter in Book/Report/Conference proceedingChapter

9 Scopus citations

Abstract

Research in the last several years has shown that Notch proteolysis, and thus Notch activation, is conformationally controlled by the extracellular juxtamembrane NRR of Notch, which sterically occludes the S2 protease site until ligand binds. The question of how conformational exposure of the protease site is achieved during physiologic activation, and thus how normal activation is bypassed in disease pathogenesis, has been the subject of intense study in the last several years, and is the subject of this chapter. Here, we summarize the structural features of the NRR domains of Notch receptors that establish the autoinhibited state and then review a number of recent studies aimed at testing the mechanotransduction model for Notch signaling using force spectroscopy and molecular tension sensors.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages47-58
Number of pages12
DOIs
StatePublished - Jan 1 2018

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1066
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Mechanotransduction
  • Molecular tension sensors
  • Notch signaling
  • Single molecule force spectroscopy
  • X-ray structure

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