PDBsum entry 4b3g

Hydrolase/RNA

PDB id: 4b3g

Contents

Protein chain

614 a.a.

DNA/RNA

Waters ×145

PDB id:

4b3g

Name:

Hydrolase/RNA

Title:

Crystal structure of ighmbp2 helicase in complex with RNA

Structure:

DNA-binding protein smubp-2. Chain: a, b. Fragment: residues 3-648. Synonym: ighmbp2, atp-dependent helicase ighmbp2, glial factor 1, gf- 1, immunoglobulin mu-binding protein 2. Engineered: yes. RNA (5'-(ap Ap Ap Ap Ap Ap Ap Ap Ap)-3'). Chain: g, h. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_variant: rosetta. Synthetic: yes

Resolution:

2.85Å R-factor: 0.211 R-free: 0.292

Authors:

S.C.Lim,H.Song

Key ref:

S.C.Lim et al. (2012). The Ighmbp2 helicase structure reveals the molecular basis for disease-causing mutations in DMSA1. Nucleic Acids Res, 40, 11009-11022. PubMed id: 22965130

Date:

24-Jul-12 Release date: 26-Sep-12

Protein chains

P38935  (SMBP2_HUMAN) -  DNA-binding protein SMUBP-2 from Homo sapiens

Seq: 993 a.a.

Struc: 614 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chains

A-A-A-A-A-A-A-A-A 9 bases

A-A-A-A-A-A-A-A 8 bases

Enzyme reactions

• Enzyme class 1: E.C.3.6.4.12 - Dna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺
• Enzyme class 2: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Nucleic Acids Res 40:11009-11022 (2012)

PubMed id: 22965130

The Ighmbp2 helicase structure reveals the molecular basis for disease-causing mutations in DMSA1.

S.C.Lim, M.W.Bowler, T.F.Lai, H.Song.

ABSTRACT

Mutations in immunoglobulin µ-binding protein 2 (Ighmbp2) cause distal spinal muscular atrophy type 1 (DSMA1), an autosomal recessive disease that is clinically characterized by distal limb weakness and respiratory distress. However, despite extensive studies, the mechanism of disease-causing mutations remains elusive. Here we report the crystal structures of the Ighmbp2 helicase core with and without bound RNA. The structures show that the overall fold of Ighmbp2 is very similar to that of Upf1, a key helicase involved in nonsense-mediated mRNA decay. Similar to Upf1, domains 1B and 1C of Ighmbp2 undergo large conformational changes in response to RNA binding, rotating 30° and 10°, respectively. The RNA binding and ATPase activities of Ighmbp2 are further enhanced by the R3H domain, located just downstream of the helicase core. Mapping of the pathogenic mutations of DSMA1 onto the helicase core structure provides a molecular basis for understanding the disease-causing consequences of Ighmbp2 mutations.