Arc is a flexible modular protein capable of reversible self-oligomerization

The Biochemical Journal
Craig MyrumClive R Bramham

Abstract

The immediate early gene product Arc (activity-regulated cytoskeleton-associated protein) is posited as a master regulator of long-term synaptic plasticity and memory. However, the physicochemical and structural properties of Arc have not been elucidated. In the present study, we expressed and purified recombinant human Arc (hArc) and performed the first biochemical and biophysical analysis of hArc's structure and stability. Limited proteolysis assays and MS analysis indicate that hArc has two major domains on either side of a central more disordered linker region, consistent with in silico structure predictions. hArc's secondary structure was estimated using CD, and stability was analysed by CD-monitored thermal denaturation and differential scanning fluorimetry (DSF). Oligomerization states under different conditions were studied by dynamic light scattering (DLS) and visualized by AFM and EM. Biophysical analyses show that hArc is a modular protein with defined secondary structure and loose tertiary structure. hArc appears to be pyramid-shaped as a monomer and is capable of reversible self-association, forming large soluble oligomers. The N-terminal domain of hArc is highly basic, which may promote interaction with cytoskelet...Continue Reading

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Citations

Oct 31, 2015·Brain and Behavior·Craig MyrumClive R Bramham
Nov 23, 2017·Nature Communications·Jasmin LalondeStephen J Haggarty
Oct 10, 2018·Proteomics·Tristan Bitard-FeildelIsabelle Callebaut
Jul 4, 2017·Frontiers in Molecular Neuroscience·Agata GozdzJacek Jaworski
Sep 30, 2020·PloS One·Melissa BoldridgeLei Wang
Jul 15, 2015·The Biochemical Journal·Cameron Day, Jason D Shepherd
Oct 6, 2017·Frontiers in Behavioral Neuroscience·Francesca Managò, Francesco Papaleo
Jan 30, 2019·Frontiers in Cellular Neuroscience·Francisca Acuña-HinrichsenCarola Otth
May 30, 2017·Frontiers in Synaptic Neuroscience·Rajeevkumar R NairClive R Bramham
Sep 14, 2018·Frontiers in Synaptic Neuroscience·Yoshihisa Nakahata, Ryohei Yasuda
May 16, 2017·Frontiers in Behavioral Neuroscience·Claire E ManningAlfred J Robison
Oct 6, 2017·Frontiers in Cellular Neuroscience·Craig MyrumClive R Bramham
Jan 19, 2020·Nature Neuroscience·Vivian Budnik, Travis Thomson
Jul 14, 2020·Frontiers in Synaptic Neuroscience·Joseph P AlbanesiDavid M Jameson
Jul 4, 2017·Journal of Alzheimer's Disease : JAD·Craig MyrumTetyana Zayats
Sep 6, 2020·The European Journal of Neuroscience·Hongyu Zhang, Clive R Bramham
Mar 13, 2021·Frontiers in Cellular Neuroscience·Francisca Acuña-HinrichsenCarola Otth
Sep 25, 2017·Seminars in Cell & Developmental Biology·Jason D Shepherd
Mar 19, 2021·Biochemistry and Biophysics Reports·Erik I HallinPetri Kursula
Jun 3, 2021·Journal of Neurochemistry·Alicyia Walczyk-MooradallyJasmin Lalonde

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Methods Mentioned

BETA
PCR
AFM
chip
differential scanning calorimetry

Software Mentioned

GlobPlot2
BIAevaluation
MODBASE
Jalview
MaxQuant
MeDor
Arc
Malvern DTS
Clustal Omega
DisEMBL

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