HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: ps.041184105v1 14/5/1274    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lubman, O. Y. Articles by Korolev, S. Search for Related Content PubMed PubMed Citation Articles by Lubman, O. Y. Articles by Korolev, S. Social Bookmarking                   What's this?

The crystal structure of a partial mouse Notch-1 ankyrin domain: Repeats 4 through 7 preserve an ankyrin fold

¹ Department of Molecular Biology and Pharmacology and the Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA² Institute of Structural Molecular Biology, Birkbeck and University College London, London, WC1E 7HX, United Kingdom³ Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri 63130, USA

(RECEIVED October 22, 2004; FINAL REVISION January 21, 2005; ACCEPTED January 26, 2005)

Folding and stability of proteins containing ankyrin repeats (ARs) is of great interest because they mediate numerous protein–protein interactions involved in a wide range of regulatory cellular processes. Notch, an ankyrin domain containing protein, signals by converting a transcriptional repression complex into an activation complex. The Notch ANK domain is essential for Notch function and contains seven ARs. Here, we present the 2.2 Å crystal structure of ARs 4–7 from mouse Notch 1 (m1ANK). These C-terminal repeats were resistant to degradation during crystallization, and their secondary and tertiary structures are maintained in the absence of repeats 1–3. The crystallized fragment adopts a typical ankyrin fold including the poorly conserved seventh AR, as seen in the Drosophila Notch ANK domain (dANK). The structural preservation and stability of the C-terminal repeats shed a new light onto the mechanism of hetero-oligomeric assembly during Notch-mediated transcriptional activation.

Keywords: ankyrin repeats; Notch; crystal structure

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.041184105.

Reprint requests to: Sergey Korolev, Saint Louis University School of Medicine, Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis, MO 63130, USA; e-mail: korolevs{at}slu.edu; fax: (314) 977-9205.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				W. R. Gordon, K. L. Arnett, and S. C. Blacklow The molecular logic of Notch signaling - a structural and biochemical perspective J. Cell Sci., October 1, 2008; 121(19): 3109 - 3119. [Abstract] [Full Text] [PDF]

				H.-T. Cheng, M. Kim, M. T. Valerius, K. Surendran, K. Schuster-Gossler, A. Gossler, A. P. McMahon, and R. Kopan Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron Development, February 15, 2007; 134(4): 801 - 811. [Abstract] [Full Text] [PDF]

				M. Ehebauer, P. Hayward, and A. Martinez-Arias Notch Signaling Pathway Sci. Signal., December 5, 2006; 2006(364): cm7 - cm7. [Abstract] [Full Text] [PDF]

				C.-T. Ong, H.-T. Cheng, L.-W. Chang, T. Ohtsuka, R. Kageyama, G. D. Stormo, and R. Kopan Target Selectivity of Vertebrate Notch Proteins: COLLABORATION BETWEEN DISCRETE DOMAINS AND CSL-BINDING SITE ARCHITECTURE DETERMINES ACTIVATION PROBABILITY J. Biol. Chem., February 24, 2006; 281(8): 5106 - 5119. [Abstract] [Full Text] [PDF]