University of Oulu

Hallin EI, Markússon S, Böttger L, Torda AE, Bramham CR, Kursula P (2021) Crystal and solution structures reveal oligomerization of individual capsid homology domains of Drosophila Arc. PLoS ONE 16(5): e0251459. https://doi.org/10.1371/journal.pone.0251459

Crystal and solution structures reveal oligomerization of individual capsid homology domains of Drosophila Arc

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Author: Hallin, Erik I.1; Markússon, Sigurbjörn1; Böttger, Lev2;
Organizations: 1Department of Biomedicine, University of Bergen, Bergen, Norway
2Centre for Bioinformatics (ZBH), University of Hamburg, Hamburg, Germany
3KG Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, Bergen, Norway
4Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021070741239
Language: English
Published: Public Library of Science, 2021
Publish Date: 2021-07-07
Description:

Abstract

Synaptic plasticity is vital for brain function and memory formation. One of the key proteins in long-term synaptic plasticity and memory is the activity-regulated cytoskeleton-associated protein (Arc). Mammalian Arc forms virus-like capsid structures in a process requiring the N-terminal domain and contains two C-terminal lobes that are structural homologues to retroviral capsids. Drosophila has two isoforms of Arc, dArc1 and dArc2, with low sequence similarity to mammalian Arc, but lacking a large N-terminal domain. Both dArc isoforms are related to the Ty3/gypsy retrotransposon capsid, consisting of N- and C-terminal lobes. Structures of dArc1, as well as capsids formed by both dArc isoforms, have been recently determined. We carried out structural characterization of the four individual dArc lobe domains. As opposed to the corresponding mammalian Arc lobe domains, which are monomeric, the dArc lobes were all oligomeric in solution, indicating a strong propensity for homophilic interactions. A truncated N-lobe from dArc2 formed a domain-swapped dimer in the crystal structure, resulting in a novel dimer interaction that could be relevant for capsid assembly or other dArc functions. This domain-swapped structure resembles the dimeric protein C of flavivirus capsids, as well as the structure of histones dimers, domain-swapped transcription factors, and membrane-interacting BAK domains. The strong oligomerization properties of the isolated dArc lobe domains explain the ability of dArc to form capsids in the absence of any large N-terminal domain, in contrast to the mammalian protein.

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 16
Issue: 5
Article number: e0251459
DOI: 10.1371/journal.pone.0251459
OADOI: https://oadoi.org/10.1371/journal.pone.0251459
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Subjects:
Funding: The research leading to this result has been supported by the project CALIPSOplus under the Grant Agreement 730872, as well as by iNEXT, grant number 653706, from the EU Framework Programme for Research and Innovation HORIZON 2020. This work was supported by a Research Council of Norway TOPPFORSK grant (249951) to CRB, a Research Council of Norway INFRASTRUCTURE grant (245828), and a grant from the Meltzer Foundation to PK.
Copyright information: © 2021 Hallin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  https://creativecommons.org/licenses/by/4.0/