4KIT: Crystal Structure Of Human Brr2 In Complex With The Prp8 Jab1/mpn Domain

Citation:
Abstract
The Ski2-like RNA helicase Brr2 is a core component of the spliceosome that must be tightly regulated to ensure correct timing of spliceosome activation. Little is known about mechanisms of regulation of Ski2-like helicases by protein cofactors. Here we show by crystal structure and biochemical analyses that the Prp8 protein, a major regulator of the spliceosome, can insert its C-terminal tail into Brr2's RNA-binding tunnel, thereby intermittently blocking Brr2's RNA-binding, adenosine triphosphatase, and U4/U6 unwinding activities. Inefficient Brr2 repression is the only recognizable phenotype associated with certain retinitis pigmentosa-linked Prp8 mutations that map to its C-terminal tail. Our data show how a Ski2-like RNA helicase can be reversibly inhibited by a protein cofactor that directly competes with RNA substrate binding.
PDB ID: 4KITDownload
MMDB ID: 110757
PDB Deposition Date: 2013/5/2
Updated in MMDB: 2013/08
Experimental Method:
x-ray diffraction
Resolution: 3.6  Å
Source Organism:
Similar Structures:
Biological Unit for 4KIT: dimeric; determined by author and by software (PISA)
Molecular Components in 4KIT
Label Count Molecule
Proteins (2 molecules)
1
U5 Small Nuclear Ribonucleoprotein 200 KDA Helicase(Gene symbol: SNRNP200)
Molecule annotation
1
Pre-mrna-processing-splicing Factor 8(Gene symbol: PRPF8)
Molecule annotation
Chemicals (3 molecules)
1
2
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.