PDBsum entry 4jvh

RNA binding protein

PDB id: 4jvh

Contents

Protein chain

176 a.a.

DNA/RNA

Ligands

SO4 ×2

PDB id:

4jvh

Name:

RNA binding protein

Title:

Structure of the star domain of quaking protein in complex with RNA

Structure:

Protein quaking. Chain: a. Fragment: star domain. Synonym: hqk, hqki. Engineered: yes. RNA (5'-r( Up Up Cp Ap Cp Up Ap Ap Cp Ap A)-3'). Chain: d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: qki, hkq. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans

Resolution:

3.50Å R-factor: 0.250 R-free: 0.316

Authors:

M.Teplova,M.Hafner,D.Teplov,K.Essig,T.Tuschl,D.J.Patel

Key ref:

M.Teplova et al. (2013). Structure-function studies of STAR family Quaking proteins bound to their in vivo RNA target sites. Genes Dev, 27, 928-940. PubMed id: 23630077 DOI: 10.1101/gad.216531.113

Date:

25-Mar-13 Release date: 08-May-13

Protein chain

Q96PU8  (QKI_HUMAN) -  KH domain-containing RNA-binding protein QKI from Homo sapiens

Seq: 341 a.a.

Struc: 176 a.a.

DNA/RNA chain

A-C-U-A-A-C-A-A 8 bases

DOI no: 10.1101/gad.216531.113

Genes Dev 27:928-940 (2013)

PubMed id: 23630077

Structure-function studies of STAR family Quaking proteins bound to their in vivo RNA target sites.

M.Teplova, M.Hafner, D.Teplov, K.Essig, T.Tuschl, D.J.Patel.

ABSTRACT

Mammalian Quaking (QKI) and its Caenorhabditis elegans homolog, GLD-1 (defective in germ line development), are evolutionarily conserved RNA-binding proteins, which post-transcriptionally regulate target genes essential for developmental processes and myelination. We present X-ray structures of the STAR (signal transduction and activation of RNA) domain, composed of Qua1, K homology (KH), and Qua2 motifs of QKI and GLD-1 bound to high-affinity in vivo RNA targets containing YUAAY RNA recognition elements (RREs). The KH and Qua2 motifs of the STAR domain synergize to specifically interact with bases and sugar-phosphate backbones of the bound RRE. Qua1-mediated homodimerization generates a scaffold that enables concurrent recognition of two RREs, thereby plausibly targeting tandem RREs present in many QKI-targeted transcripts. Structure-guided mutations reduced QKI RNA-binding affinity in vitro and in vivo, and expression of QKI mutants in human embryonic kidney cells (HEK293) significantly decreased the abundance of QKI target mRNAs. Overall, our studies define principles underlying RNA target selection by STAR homodimers and provide insights into the post-transcriptional regulatory function of mammalian QKI proteins.