Evidence map›Paper›PMID 31853358›Full record

ArticleChemical science2019

Investigation of GTP-dependent dimerization of G12X K-Ras variants using ultraviolet photodissociation mass spectrometry.

M Rachel Mehaffey, Christopher L Schardon, Elisa T Novelli, Michael B Cammarata, Lauren J Webb, Walter Fast, Jennifer S Brodbelt

Open access · diamondAbstract read
In one paragraph

Article in Chemical science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. A Conformation-Specific Approach to Native Top-down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024
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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

7 authors at 2 institutions in 2 countries.

M Rachel MehaffeyDepartment of Chemistry , University of Texas at Austin , Austin , TX 78712-0165 , USA . Email: jbrodbelt@cm.utexas.edu ; Tel: +1-512-471-0028.
Christopher L SchardonDivision of Chemical Biology and Medicinal Chemistry , College of Pharmacy , University of Texas at Austin , Austin , TX 78712 , USA.
Elisa T NovelliDepartment of Chemistry , University of Texas at Austin , Austin , TX 78712-0165 , USA . Email: jbrodbelt@cm.utexas.edu ; Tel: +1-512-471-0028.ORCID 0000-0002-4046-1229
Michael B CammarataDepartment of Chemistry , University of Texas at Austin , Austin , TX 78712-0165 , USA . Email: jbrodbelt@cm.utexas.edu ; Tel: +1-512-471-0028.
Lauren J WebbDepartment of Chemistry , University of Texas at Austin , Austin , TX 78712-0165 , USA . Email: jbrodbelt@cm.utexas.edu ; Tel: +1-512-471-0028.
Walter FastDivision of Chemical Biology and Medicinal Chemistry , College of Pharmacy , University of Texas at Austin , Austin , TX 78712 , USA.
Jennifer S BrodbeltDepartment of Chemistry , University of Texas at Austin , Austin , TX 78712-0165 , USA . Email: jbrodbelt@cm.utexas.edu ; Tel: +1-512-471-0028.ORCID 0000-0003-3207-0217
The University of Texas at Austin · USInstitute of Medicinal Plant Development · CN

Funding

UVPD Mass Spectrometry of Protein ComplexesR01GM121714 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI BRODBELT, JENNIFER S. · 2017 to 2020
$1.4M
NIGMS NIH HHS R01 GM121714
6 · The paper itself

Abstract

Mutations in the GTPase enzyme K-Ras, specifically at codon G12, remain the most common genetic alterations in human cancers. The mechanisms governing activation of downstream signaling pathways and how they relate back to the identity of the mutation have yet to be completely defined. Here we use native mass spectrometry (MS) combined with ultraviolet photodissociation (UVPD) to investigate the impact of three G12X mutations (G12C, G12V, G12S) on the homodimerization of K-Ras as well as heterodimerization with a downstream effector protein, Raf. Electrospray ionization (ESI) was used to transfer complexes of WT or G12X K-Ras bound to guanosine 5'-diphosphate (GDP) or GppNHp (non-hydrolyzable analogue of GTP) into the gas phase. Relative abundances of homo- or hetero-dimer complexes were estimated from ESI-MS spectra. K-Ras + Raf heterocomplexes were activated with UVPD to probe structural changes responsible for observed differences in the amount of heterocomplex formed for each variant. Holo (ligand-bound) fragment ions resulting from photodissociation suggest the G12X mutants bind Raf along the expected effector binding region (β-interface) but may interact with Raf

Identifiers

PMID31853358
PMCPMC6837035
OpenAlexW2959130477

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Registered trials

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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.