Conformational variability of the intracellular domain of Drosophila Notch and its interaction with Suppressor of Hairless

Deb Kelly, Robert J. Lake, Thomas Walz, Spyros Artavanis-Tsakonas

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The Notch receptor is the central element in an evolutionarily conserved signal transduction pathway that controls cell fates in metazoans. Receptor-ligand interactions trigger a cascade of proteolytic events that release the entire Notch intracellular domain (NICD) from the membrane, permitting its translocation into the nucleus and participation in a transcriptionally active complex. Using electron microscopy, we examined the structure of NICD and its interaction with the DNA-binding effector of Notch signaling, Suppressor of Hairless [Su(H)]. In conjunction with biochemical analyses, we found that Drosophila NICD is monomeric and exists in two primary conformational states, only one of which can bind Su(H). Furthermore, we show that changes in divalent cation concentrations lead to NICD self-association, which seems to be mediated by the polyglutamine-containing, opa-repeat region of NICD. Our study suggests that conformational modulation of NICD may define a mechanism of Notch pathway control.

Original languageEnglish (US)
Pages (from-to)9591-9596
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number23
DOIs
StatePublished - Jun 5 2007

Fingerprint

Notch Receptors
Intracellular Membranes
Divalent Cations
Drosophila
Signal Transduction
Electron Microscopy
Ligands
DNA
polyglutamine

All Science Journal Classification (ASJC) codes

  • General

Cite this

@article{d0194d37ea22472cbd5fccd6bf82fc53,
title = "Conformational variability of the intracellular domain of Drosophila Notch and its interaction with Suppressor of Hairless",
abstract = "The Notch receptor is the central element in an evolutionarily conserved signal transduction pathway that controls cell fates in metazoans. Receptor-ligand interactions trigger a cascade of proteolytic events that release the entire Notch intracellular domain (NICD) from the membrane, permitting its translocation into the nucleus and participation in a transcriptionally active complex. Using electron microscopy, we examined the structure of NICD and its interaction with the DNA-binding effector of Notch signaling, Suppressor of Hairless [Su(H)]. In conjunction with biochemical analyses, we found that Drosophila NICD is monomeric and exists in two primary conformational states, only one of which can bind Su(H). Furthermore, we show that changes in divalent cation concentrations lead to NICD self-association, which seems to be mediated by the polyglutamine-containing, opa-repeat region of NICD. Our study suggests that conformational modulation of NICD may define a mechanism of Notch pathway control.",
author = "Deb Kelly and Lake, {Robert J.} and Thomas Walz and Spyros Artavanis-Tsakonas",
year = "2007",
month = "6",
day = "5",
doi = "10.1073/pnas.0702887104",
language = "English (US)",
volume = "104",
pages = "9591--9596",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "23",

}

Conformational variability of the intracellular domain of Drosophila Notch and its interaction with Suppressor of Hairless. / Kelly, Deb; Lake, Robert J.; Walz, Thomas; Artavanis-Tsakonas, Spyros.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 23, 05.06.2007, p. 9591-9596.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Conformational variability of the intracellular domain of Drosophila Notch and its interaction with Suppressor of Hairless

AU - Kelly, Deb

AU - Lake, Robert J.

AU - Walz, Thomas

AU - Artavanis-Tsakonas, Spyros

PY - 2007/6/5

Y1 - 2007/6/5

N2 - The Notch receptor is the central element in an evolutionarily conserved signal transduction pathway that controls cell fates in metazoans. Receptor-ligand interactions trigger a cascade of proteolytic events that release the entire Notch intracellular domain (NICD) from the membrane, permitting its translocation into the nucleus and participation in a transcriptionally active complex. Using electron microscopy, we examined the structure of NICD and its interaction with the DNA-binding effector of Notch signaling, Suppressor of Hairless [Su(H)]. In conjunction with biochemical analyses, we found that Drosophila NICD is monomeric and exists in two primary conformational states, only one of which can bind Su(H). Furthermore, we show that changes in divalent cation concentrations lead to NICD self-association, which seems to be mediated by the polyglutamine-containing, opa-repeat region of NICD. Our study suggests that conformational modulation of NICD may define a mechanism of Notch pathway control.

AB - The Notch receptor is the central element in an evolutionarily conserved signal transduction pathway that controls cell fates in metazoans. Receptor-ligand interactions trigger a cascade of proteolytic events that release the entire Notch intracellular domain (NICD) from the membrane, permitting its translocation into the nucleus and participation in a transcriptionally active complex. Using electron microscopy, we examined the structure of NICD and its interaction with the DNA-binding effector of Notch signaling, Suppressor of Hairless [Su(H)]. In conjunction with biochemical analyses, we found that Drosophila NICD is monomeric and exists in two primary conformational states, only one of which can bind Su(H). Furthermore, we show that changes in divalent cation concentrations lead to NICD self-association, which seems to be mediated by the polyglutamine-containing, opa-repeat region of NICD. Our study suggests that conformational modulation of NICD may define a mechanism of Notch pathway control.

UR - http://www.scopus.com/inward/record.url?scp=34547417977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547417977&partnerID=8YFLogxK

U2 - 10.1073/pnas.0702887104

DO - 10.1073/pnas.0702887104

M3 - Article

C2 - 17535912

AN - SCOPUS:34547417977

VL - 104

SP - 9591

EP - 9596

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 23

ER -