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Domain topology of human Rasal

  • Jorge Cuellar , José María Valpuesta , Alfred Wittinghofer und Begoña Sot EMAIL logo
Veröffentlicht/Copyright: 8. September 2017
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 399 Heft 1

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.

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

Acknowledgments

We thank Dr. Mónica Chagoyen (CNB-CSIC) for building the Ct domain model and Unidad de Proteómica of Centro Nacional de Biotecnología (CNB-CSIC) for XL-MS experiments and Catherine Mark for editorial assistance. This work was supported by Spanish Ministry of Economy and Innovation grants BFU2016-75984 (to JMV) and grants RYC-2011-08746 and Bolsa de Investigación L’Oréal-UNESCO 2013 (to BS).

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Supplemental Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2017-0159).

Received: 2017-5-3
Accepted: 2017-8-31
Published Online: 2017-9-8
Published in Print: 2017-12-20

©2018 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hsz-2017-0159
Schlagwörter für diesen Artikel
electron microscopy; GAP1 family; Rap; Ras; Rasal

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Maintaining protein composition in cilia
  4. Eremophilane-type sesquiterpenes from fungi and their medicinal potential
  5. How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways
  6. Minireviews
  7. Targeted degradomics in protein terminomics and protease substrate discovery
  8. Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2–FAM72-|
  9. Research Articles/Short Communications
  10. Protein Structure and Function
  11. Domain topology of human Rasal
  12. The consequences of deglycosylation of recombinant intra-melanosomal domain of human tyrosinase
  13. Cell Biology and Signaling
  14. Locally produced xenin and the neurotensinergic system in pancreatic islet function and β-cell survival
  15. The long non-coding RNA CRNDE promotes cervical cancer cell growth and metastasis
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