Evidence map›Paper›PMID 31981262›Full record

ArticleProtein science : a publication of the Protein Society2020

Structural and functional characterization of the dominant negative P-loop lysine mutation in the dynamin superfamily protein Vps1.

Bryan A Tornabene, Natalia V Varlakhanova, Christopher J Hosford, Joshua S Chappie, Marijn G J Ford

Open access · bronzeAbstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 37% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Upregulated small GTPase immunity-associated proteins confer resistance toFrontiers in cellular and infection microbiology · 2025
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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

5 authors at 2 institutions in 1 country.

Bryan A TornabeneDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-6879-7787
Natalia V VarlakhanovaDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-9776-4423
Christopher J HosfordDepartment of Molecular Medicine, Cornell University, Ithaca, New York.
Joshua S ChappieDepartment of Molecular Medicine, Cornell University, Ithaca, New York.ORCID 0000-0002-5733-7275
Marijn G J FordDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-9115-4413
University of Pittsburgh · USCornell University · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
The Roles of the Dynamin-Related Protein Vps1 and the ESCRT Complex in MicroautophagyR01GM120102 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FORD, MARIJN GERARD JOHANNES · 2016 to 2020
$1.5M
A low volume isothermal titration calorimeter for structure-function studies of biological macromoleculesS10OD023481 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRONENBORN, ANGELA M. · 2017 to 2017
$127k
NCI NIH HHS P30 CA047904NIGMS NIH HHS GM120102NIGMS NIH HHS R01 GM120102NIH HHS S10 OD023481
6 · The paper itself

Abstract

Dynamin-superfamily proteins (DSPs) are large self-assembling mechanochemical GTPases that harness GTP hydrolysis to drive membrane remodeling events needed for many cellular processes. Mutation to alanine of a fully conserved lysine within the P-loop of the DSP GTPase domain results in abrogation of GTPase activity. This mutant has been widely used in the context of several DSPs as a dominant-negative to impair DSP-dependent processes. However, the precise deficit of the P-loop K to A mutation remains an open question. Here, we use biophysical, biochemical and structural approaches to characterize this mutant in the context of the endosomal DSP Vps1. We show that the Vps1 P-loop K to A mutant binds nucleotide with an affinity similar to wild type but exhibits defects in the organization of the GTPase active site that explain the lack of hydrolysis. In cells, Vps1 and Dnm1 bearing the P-loop K to A mutation are defective in disassembly. These mutants become trapped in assemblies at the typical site of action of the DSP. This work provides mechanistic insight into the widely-used DSP P-loop K to A mutation and the basis of its dominant-negative effects in the cell.

Indexed as

MutationChaetomiumDynaminsFungal ProteinsLysineModels, MolecularVesicular Transport ProteinsDynaminsFungal ProteinsLysineVesicular Transport Proteins

Identifiers

PMID31981262
PMCPMC7255512
OpenAlexW3001439100

What OpenQuestion holds

Textmetadata
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.