PDBsum entry 2mdr

Hydrolase

PDB id: 2mdr

Contents

Protein chain

94 a.a.

PDB id:

2mdr

Name:

Hydrolase

Title:

Solution structure of the third double-stranded RNA-binding domain (dsrbd3) of human adenosine-deaminase adar1

Structure:

Double-stranded RNA-specific adenosine deaminase. Chain: a. Fragment: unp residues 708-801. Synonym: drada, 136 kda double-stranded RNA-binding protein, p136, interferon-inducible protein 4, ifi-4, k88dsrbp. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: adar, adar1, dsrad, g1p1, ifi4. Expressed in: escherichia coli. Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

P.Barraud,S.Banerjee,W.I.Mohamed,M.F.Jantsch,F.H.Allain

Key ref:

P.Barraud et al. (2014). 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 U S A, 111, E1852. PubMed id: 24753571 DOI: 10.1073/pnas.1323698111

Date:

17-Sep-13 Release date: 30-Apr-14

Protein chain

P55265  (DSRAD_HUMAN) -  Double-stranded RNA-specific adenosine deaminase from Homo sapiens

Seq: 1226 a.a.

Struc: 94 a.a.

Enzyme reactions

• Enzyme class: E.C.3.5.4.37 - double-stranded Rna adenine deaminase.
• Reaction: adenosine in double-stranded RNA + H2O + H⁺ = inosine in double- stranded RNA + NH4⁺

DOI no: 10.1073/pnas.1323698111

Proc Natl Acad Sci U S A 111:E1852 (2014)

PubMed id: 24753571

A bimodular nuclear localization signal assembled via an extended double-stranded RNA-binding domain acts as an RNA-sensing signal for transportin 1.

P.Barraud, S.Banerjee, W.I.Mohamed, M.F.Jantsch, F.H.Allain.

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.