4B3F

crystal structure of Ighmbp2 helicase

Summary for 4B3F

• Entry DOI: 10.2210/pdb4b3f/pdb
• Related: 1MSZ 4B3G
• Descriptor: DNA-BINDING PROTEIN SMUBP-2, PHOSPHATE ION (3 entities in total)
• Functional Keywords: hydrolase, helicase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus : P38935
• Total number of polymer chains: 1
• Total formula weight: 71722.94

Authors

Lim, S.C.,Song, H. (deposition date: 2012-07-24, release date: 2012-09-26, Last modification date: 2024-05-08)

Primary citation

Lim, S.C.,Bowler, M.W.,Lai, T.F.,Song, H.
The Ighmbp2 Helicase Structure Reveals the Molecular Basis for Disease-Causing Mutations in Dmsa1.
Nucleic Acids Res., 40:11009-, 2012

PubMed 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.

PubMed: 22965130
DOI: 10.1093/NAR/GKS792

Experimental method

X-RAY DIFFRACTION (2.5 Å)