2MDR

Solution structure of the third double-stranded RNA-binding domain (dsRBD3) of human adenosine-deaminase ADAR1

Summary for 2MDR

• Entry DOI: 10.2210/pdb2mdr/pdb
• NMR Information: BMRB: 19502
• Descriptor: Double-stranded RNA-specific adenosine deaminase (1 entity in total)
• Functional Keywords: deaminase, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Cytoplasm. Isoform 5: Cytoplasm: P55265
• Total number of polymer chains: 1
• Total formula weight: 12492.19

Authors

Barraud, P.,Banerjee, S.,Mohamed, W.I.,Jantsch, M.F.,Allain, F.H. (deposition date: 2013-09-17, release date: 2014-04-30, Last modification date: 2024-05-15)

Primary citation

Barraud, P.,Banerjee, S.,Mohamed, W.I.,Jantsch, M.F.,Allain, F.H.
A bimodular nuclear localization signal assembled via an extended double-stranded RNA-binding domain acts as an RNA-sensing signal for transportin 1.
Proc.Natl.Acad.Sci.USA, 111:E1852-E1861, 2014

PubMed Abstract: The human RNA-editing enzyme adenosine deaminase acting on RNA (ADAR1) carries a unique nuclear localization signal (NLS) that overlaps one of its double-stranded RNA-binding domains (dsRBDs). This dsRBD-NLS is recognized by the nuclear import receptor transportin 1 (Trn1; also called karyopherin-β2) in an RNA-sensitive manner. Most Trn1 cargos bear a well-characterized proline-tyrosine-NLS, which is missing from the dsRBD-NLS. Here, we report the structure of the dsRBD-NLS, which reveals an unusual dsRBD fold extended by an additional N-terminal α-helix that brings the N- and C-terminal flanking regions in close proximity. We demonstrate experimentally that the atypical ADAR1-NLS is bimodular and is formed by the combination of the two flexible fragments flanking the folded domain. The intervening dsRBD acts only as an RNA-sensing scaffold, allowing the two NLS modules to be properly positioned for interacting with Trn1. We also provide a structural model showing how Trn1 can recognize the dsRBD-NLS and how dsRNA binding can interfere with Trn1 binding.

PubMed: 24753571
DOI: 10.1073/pnas.1323698111

Experimental method

SOLUTION NMR