KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation

Timothy H. Tran; Albert H. Chan; Lucy C. Young; Lakshman Bindu; Chris Neale; Simon Messing; Srisathiyanarayanan Dharmaiah; Troy Taylor; John-Paul Denson; Dominic Esposito; Dwight V. Nissley; Andrew G. Stephen; Frank McCormick; Dhirendra K. Simanshu

doi:10.1038/s41467-021-21422-x

Nature Communications (Feb 2021)

KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation

Timothy H. Tran,
Albert H. Chan,
Lucy C. Young,
Lakshman Bindu,
Chris Neale,
Simon Messing,
Srisathiyanarayanan Dharmaiah,
Troy Taylor,
John-Paul Denson,
Dominic Esposito,
Dwight V. Nissley,
Andrew G. Stephen,
Frank McCormick,
Dhirendra K. Simanshu

Affiliations

Timothy H. Tran: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
Albert H. Chan: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
Lucy C. Young: Helen Diller Family Comprehensive Cancer Center, University of California
Lakshman Bindu: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
Chris Neale: Theoretical Biology and Biophysics, Los Alamos National Laboratory
Simon Messing: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
Srisathiyanarayanan Dharmaiah: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
Troy Taylor: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
John-Paul Denson: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
Dominic Esposito: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
Dwight V. Nissley: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
Andrew G. Stephen: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
Frank McCormick: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
Dhirendra K. Simanshu: NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.

DOI: https://doi.org/10.1038/s41467-021-21422-x
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 16

Abstract

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The molecular details of the RAS-RAF interaction are still not fully understood. Here, the authors present crystal structures of wild-type and mutant KRAS in complex with the RAS-binding and membrane-interacting cysteine-rich domains of RAF1, and propose a model of the membrane-bound RAS-RAF complex.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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