1H, 15 N and 13 C backbone assignment of apo TDP-43 RNA recognition motifs

David D. Scott, Liberty Francois-Moutal, Vlad K. Kumirov, May Khanna

Research output: Contribution to journalArticle

Abstract

TAR DNA-binding protein 43 (TDP-43) is a ubiquitously expressed nuclear protein that influences diverse cellular processes by regulating alternative splicing of RNA and microRNA biogenesis. It is also a pathological protein found in sporadic ALS and in the most common subtype of frontotemporal lobar degeneration with ubiquitinated inclusions (FLTD-U). TDP-43 has two tandem RNA-binding domains, RRM1 and RRM2. The NMR structure of TDP-43 was solved in the presence of UG-rich RNA sequences bound to the RRM1 and RRM2 domains. Here we report the backbone assignment of apo TDP-43. The chemical shift (HN, N, C, Cα and Cβ) analysis shows the predicted regions of secondary structure are in good agreement with those observed for TDP-43 in complex with RNA. However, our data show that the apo structure of TPD-43 has increased flexibility in the regions that would normally have been used to anchor the RNA bases. The backbone chemical shifts assignments will prove useful in the study of TDP-43 interaction with non-canonical RNA and RRM-binding proteins.

Original languageEnglish (US)
Pages (from-to)163-167
Number of pages5
JournalBiomolecular NMR assignments
Volume13
Issue number1
DOIs
StatePublished - Apr 1 2019

Fingerprint

DNA-Binding Proteins
RNA
Chemical shift
Frontotemporal Lobar Degeneration
RNA-Binding Proteins
Alternative Splicing
Temperature programmed desorption
Nuclear Proteins
Anchors
MicroRNAs
RNA Recognition Motif
Carrier Proteins
Nuclear magnetic resonance
Proteins

Keywords

  • Chemical shift assignment
  • HSQC
  • NMR
  • RNA recognition motif
  • Secondary structure
  • TDP-43

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry

Cite this

1H, 15 N and 13 C backbone assignment of apo TDP-43 RNA recognition motifs . / Scott, David D.; Francois-Moutal, Liberty; Kumirov, Vlad K.; Khanna, May.

In: Biomolecular NMR assignments, Vol. 13, No. 1, 01.04.2019, p. 163-167.

Research output: Contribution to journalArticle

Scott, David D. ; Francois-Moutal, Liberty ; Kumirov, Vlad K. ; Khanna, May. / 1H, 15 N and 13 C backbone assignment of apo TDP-43 RNA recognition motifs In: Biomolecular NMR assignments. 2019 ; Vol. 13, No. 1. pp. 163-167.
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