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The Ras switch in structural and historical perspective

Authors
  • Gasper, Raphael1
  • Wittinghofer, Fred1
  • 1 Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Str. 11 , (Germany)
Type
Published Article
Journal
Biological Chemistry
Publisher
Walter de Gruyter GmbH
Publication Date
Nov 07, 2019
Volume
401
Issue
1
Pages
143–163
Identifiers
DOI: 10.1515/hsz-2019-0330
Source
De Gruyter
Keywords
License
Yellow

Abstract

Since its discovery as an oncogene more than 40 years ago, Ras has been and still is in the focus of many academic and pharmaceutical labs around the world. A huge amount of work has accumulated on its biology. However, many questions about the role of the different Ras isoforms in health and disease still exist and a full understanding will require more intensive work in the future. Here we try to survey some of the structural findings in a historical perspective and how it has influenced our understanding of structure-function and mechanistic relationships of Ras and its interactions. The structures show that Ras is a stable molecular machine that uses the dynamics of its switch regions for the interaction with all regulators and effectors. This conformational flexibility has been used to create small molecule drug candidates against this important oncoprotein.

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