4BGD

Crystal structure of Brr2 in complex with the Jab1/MPN domain of Prp8

Summary for 4BGD

• Entry DOI: 10.2210/pdb4bgd/pdb
• Descriptor: PRE-MRNA-SPLICING HELICASE BRR2, PRE-MRNA-SPLICING FACTOR 8, ADENOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: transcription, spliceosome, rna helicase, u5 snrnp, retinitis pigmentosa
• Biological source: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST); More
• Cellular location: Nucleus (Probable): P32639; Nucleus: P33334
• Total number of polymer chains: 2
• Total formula weight: 224760.37

Authors

Nguyen, T.H.D.,Li, J.,Nagai, K. (deposition date: 2013-03-25, release date: 2013-05-29, Last modification date: 2023-12-20)

Primary citation

Nguyen, T.H.D.,Li, J.,Galej, W.P.,Oshikane, H.,Newman, A.J.,Nagai, K.
Structural Basis of Brr2-Prp8 Interactions and Implications for U5 Snrnp Biogenesis and the Spliceosome Active Site
Structure, 21:910-, 2013

PubMed Abstract: The U5 small nuclear ribonucleoprotein particle (snRNP) helicase Brr2 disrupts the U4/U6 small nuclear RNA (snRNA) duplex and allows U6 snRNA to engage in an intricate RNA network at the active center of the spliceosome. Here, we present the structure of yeast Brr2 in complex with the Jab1/MPN domain of Prp8, which stimulates Brr2 activity. Contrary to previous reports, our crystal structure and mutagenesis data show that the Jab1/MPN domain binds exclusively to the N-terminal helicase cassette. The residues in the Jab1/MPN domain, whose mutations in human Prp8 cause the degenerative eye disease retinitis pigmentosa, are found at or near the interface with Brr2, clarifying its molecular pathology. In the cytoplasm, Prp8 forms a precursor complex with U5 snRNA, seven Smproteins, Snu114, and Aar2, but after nuclear import, Brr2 replaces Aar2 to form mature U5 snRNP. Our structure explains why Aar2 and Brr2 are mutually exclusive and provides important insights into the assembly of U5 snRNP.

PubMed: 23727230
DOI: 10.1016/J.STR.2013.04.017

Experimental method

X-RAY DIFFRACTION (3.1 Å)