PDBsum entry 4kit

RNA binding protein

PDB id: 4kit

Contents

Protein chains

1722 a.a.

269 a.a.

Ligands

ADP ×2

Metals

_MG

PDB id:

4kit

Name:

RNA binding protein

Title:

Crystal structure of human brr2 in complex with the prp8 jab1/mpn domain

Structure:

U5 small nuclear ribonucleoprotein 200 kda helicase. Chain: b. Fragment: helicase region (unp residues 395-2129). Synonym: brr2 protein, activating signal cointegrator 1 complex subunit 3-like 1, brr2 homolog, u5 snrnp-specific 200 kda protein, u5-200kd. Engineered: yes. Pre-mRNA-processing-splicing factor 8. Chain: c.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: snrnp200, ascc3l1, helic2, kiaa0788. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: prpf8, prpc8. Expression_system_taxid: 7108

Resolution:

3.60Å R-factor: 0.199 R-free: 0.235

Authors:

M.C.Wahl,T.Wandersleben,K.F.Santos

Key ref:

S.Mozaffari-Jovin et al. (2013). Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8. Science, 341, 80-84. PubMed id: 23704370 DOI: 10.1126/science.1237515

Date:

02-May-13 Release date: 05-Jun-13

Protein chain

O75643  (U520_HUMAN) -  U5 small nuclear ribonucleoprotein 200 kDa helicase from Homo sapiens

Seq: 2136 a.a.

Struc: 1722 a.a.

Protein chain

Q6P2Q9  (PRP8_HUMAN) -  Pre-mRNA-processing-splicing factor 8 from Homo sapiens

Seq: 2335 a.a.

Struc: 269 a.a.

Enzyme reactions

• Enzyme class: Chain B: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

ATP + H2O = ADP (Bound ligand (Het Group name = ADP) corresponds exactly) + phosphate + H(+)

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

reference

DOI no: 10.1126/science.1237515

Science 341:80-84 (2013)

PubMed id: 23704370

Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8.

S.Mozaffari-Jovin, T.Wandersleben, K.F.Santos, C.L.Will, R.Lührmann, M.C.Wahl.

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.