Structural and mutational analysis reveals that CTNNBL1 binds NLSs in a manner distinct from that of its closest armadillo‐relative, karyopherin α. Issue 1 (20th November 2013)

• Record Type: Journal Article
• Authors: Ganesh, Karuna; van Maldegem, Febe; Telerman, Stephanie B.; Simpson, Paul; Johnson, Christopher M.; Williams, Roger L.; Neuberger, Michael S.; Rada, Cristina
• Is Part Of: FEBS letters. Volume 588:Issue 1(2014)
• Page Start: 21
• Page End: 27
• Publication Date: 2013-11-20
• Subjects: Splicing -- Nuclear import -- Armadillo domain; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.11.013
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : CTNNBL1 is a spliceosome‐associated protein that binds nuclear localization signals (NLSs) in splice factors CDC5L and Prp31 as well as the antibody diversifying enzyme AID. Here, crystal structures of human CTNNBL1 reveal a distinct structure from its closest homologue karyopherin‐α. CTNNBL1 comprises a HEAT‐like domain (including a nuclear export signal), a central armadillo domain, and a coiled‐coil C‐terminal domain. Structure‐guided mutations of the region homologous to the karyopherin‐α NLS‐binding site fail to disrupt CTNNBL1–NLS interactions. Our results identify CTNNBL1 as a unique selective NLS‐binding protein with striking differences from karyopherin‐αs. Abstract : The structure of CTNNBL1 includes an abbreviated armadillo domain. CTNNBL1 is a novel NLS binding protein with a unique carboxy‐terminal structure. Structure‐based mutagenesis of CTNNBL1 shows NLS binding distinct from karyopherins.