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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

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1437-4315
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Volume 399, Issue 1

Issues

Domain topology of human Rasal

Jorge Cuellar
  • Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain
  • Other articles by this author:
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/ José María Valpuesta
  • Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain
  • Unidad Asociada de Nanobiotecnología (CNB-CSIC e IMDEA Nanociencia), Madrid, Spain
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Alfred Wittinghofer
  • Department of Structural Biology, Max-Planck-Institute for Molecular Physiology, Dortmund, Germany
  • Other articles by this author:
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/ Begoña Sot
  • Corresponding author
  • Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain
  • Unidad Asociada de Nanobiotecnología (CNB-CSIC e IMDEA Nanociencia), Madrid, Spain
  • IMDEA-Nanociencia, Faraday 9, Campus Universitario de Cantoblanco, 28048 Madrid, Spain
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-09-08 | DOI: https://doi.org/10.1515/hsz-2017-0159

Abstract

Rasal is a modular multi-domain protein of the GTPase-activating protein 1 (GAP1) family; its four known members, GAP1m, Rasal, GAP1IP4BP and Capri, have a Ras GTPase-activating domain (RasGAP). This domain supports the intrinsically slow GTPase activity of Ras by actively participating in the catalytic reaction. In the case of Rasal, GAP1IP4BP and Capri, their remaining domains are responsible for converting the RasGAP domains into dual Ras- and Rap-GAPs, via an incompletely understood mechanism. Although Rap proteins are small GTPase homologues of Ras, their catalytic residues are distinct, which reinforces the importance of determining the structure of full-length GAP1 family proteins. To date, these proteins have not been crystallized, and their size is not adequate for nuclear magnetic resonance (NMR) or for high-resolution cryo-electron microscopy (cryoEM). Here we present the low resolution structure of full-length Rasal, obtained by negative staining electron microscopy, which allows us to propose a model of its domain topology. These results help to understand the role of the different domains in controlling the dual GAP activity of GAP1 family proteins.

This article offers supplementary material which is provided at the end of the article.

Keywords: electron microscopy; GAP1 family; Rap; Ras; Rasal

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About the article

Received: 2017-05-03

Accepted: 2017-08-31

Published Online: 2017-09-08

Published in Print: 2017-12-20


Citation Information: Biological Chemistry, Volume 399, Issue 1, Pages 63–72, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2017-0159.

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