Evidence map›Paper›PMID 33608534›Full record

ArticleNature communications2021

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 and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed, 1 pooled it
14.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

139 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.

  1. Pooled it
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  11. Review
  12. Characterization of KRASNature communications · 2026
    Article
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79 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Timothy H Tran *NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Albert H Chan *NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Lucy C Young *Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
Lakshman BinduNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Chris NealeTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Simon MessingNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Srisathiyanarayanan DharmaiahNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.ORCID 0000-0001-7630-3962
Troy TaylorNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
John-Paul DensonNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Dominic EspositoNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.ORCID 0000-0002-9987-1687
Dwight V NissleyNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.ORCID 0000-0001-7523-116X
Andrew G StephenNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Frank McCormickNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. frank.mccormick@ucsf.edu.ORCID 0000-0002-6619-7120
Dhirendra K SimanshuNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. dhirendra.simanshu@fnlcr.nih.gov.ORCID 0000-0002-9717-4618
Leidos (United States) · USLos Alamos National Laboratory · USUniversity of California, San Francisco · US

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI MALCOLM S. CAPEL · 2018 to 2026
$34.2M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENIGMS NIH HHS P30 GM124165NIH HHS S10 OD021527
6 · The paper itself

Abstract

The first step of RAF activation involves binding to active RAS, resulting in the recruitment of RAF to the plasma membrane. To understand the molecular details of RAS-RAF interaction, we present crystal structures of wild-type and oncogenic mutants of KRAS complexed with the RAS-binding domain (RBD) and the membrane-interacting cysteine-rich domain (CRD) from the N-terminal regulatory region of RAF1. Our structures reveal that RBD and CRD interact with each other to form one structural entity in which both RBD and CRD interact extensively with KRAS. Mutations at the KRAS-CRD interface result in a significant reduction in RAF1 activation despite only a modest decrease in binding affinity. Combining our structures and published data, we provide a model of RAS-RAF complexation at the membrane, and molecular insights into RAS-RAF interaction during the process of RAS-mediated RAF activation.

Indexed as

Binding SitesCrystallography, X-RayCysteineHumansModels, MolecularProtein BindingProtein ConformationProtein DomainsProtein Interaction Domains and MotifsProto-Oncogene Proteins c-rafProto-Oncogene Proteins p21(ras)ras ProteinsCysteineKRAS protein, humanProto-Oncogene Proteins c-rafProto-Oncogene Proteins p21(ras)Raf1 protein, humanras Proteins

Identifiers

PMID33608534
PMCPMC7895934
OpenAlexW3131852822

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.