The Disordered Spindly C-terminus Interacts with RZZ Subunits ROD-1 and ZWL-1 in the Kinetochore through the Same Sites in C. Elegans.

Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / chemistry Dyneins / chemistry Humans Intrinsically Disordered Proteins / chemistry Kinetochores / chemistry Magnetic Resonance Spectroscopy Protein Binding Protein Conformation Protein Interaction Domains and Motifs Repressor Proteins / chemistry Spindle Apparatus / metabolism Structure-Activity Relationship
Intrinsically disordered protein Nuclear magnetic resonance ROD/ZW10/ZWILCH RZZ Spindly

Journal

Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R

Informations de publication

Date de publication:
19 02 2021
Historique:
received: 28 10 2020
revised: 29 12 2020
accepted: 31 12 2020
pubmed: 16 1 2021
medline: 24 4 2021
entrez: 15 1 2021
Statut: ppublish

Résumé

Spindly is a dynein adaptor involved in chromosomal segregation during cell division. While Spindly's N-terminal domain binds to the microtubule motor dynein and its activator dynactin, the C-terminal domain (Spindly-C) binds its cargo, the ROD/ZW10/ZWILCH (RZZ) complex in the outermost layer of the kinetochore. In humans, Spindly-C binds to ROD, while in C. elegans Spindly-C binds to both Zwilch (ZWL-1) and ROD-1. Here, we employed various biophysical techniques to characterize the structure, dynamics and interaction sites of C. elegans Spindly-C. We found that despite the overall disorder, there are two regions with variable α-helical propensity. One of these regions is located in the C-terminal half and is compact; the second is sparsely populated in the N-terminal half. The interactions with both ROD-1 and ZWL-1 are mostly mediated by the same two sequentially remote disordered segments of Spindly-C, which are C-terminally adjacent to the helical regions. The findings suggest that the Spindly-C binding sites on ROD-1 in the ROD-1/ZWL-1 complex context are either shielded or conformationally weakened by the presence of ZWL-1 such that only ZWL-1 directly interacts with Spindly-C in C. elegans.

Identifiants

DOI: 10.1016/j.jmb.2021.166812 PMID: 33450249 PMC: PMC7870574
pubmed: 33450249
pii: S0022-2836(21)00006-1
doi: 10.1016/j.jmb.2021.166812
pmc: PMC7870574
mid: NIHMS1664410
pii:
doi:

Substances chimiques

Caenorhabditis elegans Proteins 0
Intrinsically Disordered Proteins 0
Repressor Proteins 0
Dyneins EC 3.6.4.2

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

166812

Subventions

Organisme : NCI NIH HHS
ID : P30 CA046934
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM083127
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM130694
Pays : United States
Organisme : NIH HHS
ID : S10 OD025020
Pays : United States

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Auteurs

Morkos A Henen (MA)

University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics, 12801 East 17th Avenue, Aurora, Colorado 80045, USA; Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.

Walter Myers (W)

University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics, 12801 East 17th Avenue, Aurora, Colorado 80045, USA; Anderson University, Department of Chemistry and Biology, 316 Boulevard, Anderson, SC 29621, USA.

Lauren R Schmitt (LR)

University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics, 12801 East 17th Avenue, Aurora, Colorado 80045, USA.

Kristen J Wade (KJ)

University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics, 12801 East 17th Avenue, Aurora, Colorado 80045, USA.

Alexandra Born (A)

University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics, 12801 East 17th Avenue, Aurora, Colorado 80045, USA.

Parker J Nichols (PJ)

University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics, 12801 East 17th Avenue, Aurora, Colorado 80045, USA.

Beat Vögeli (B)

University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics, 12801 East 17th Avenue, Aurora, Colorado 80045, USA. Electronic address: beat.vogeli@cuanschutz.edu.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › The Disordered Spindly C-terminus Interacts...
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