Structural and mutational analysis reveals that CTNNBL1 binds NLSs in a manner distinct from that of its closest armadillo-relative, karyopherin α☆
نویسندگان
چکیده
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.
منابع مشابه
CTNNBL1 Is a Novel Nuclear Localization Sequence-binding Protein That Recognizes RNA-splicing Factors CDC5L and Prp31
Nuclear proteins typically contain short stretches of basic amino acids (nuclear localization sequences; NLSs) that bind karyopherin α family members, directing nuclear import. Here, we identify CTNNBL1 (catenin-β-like 1), an armadillo motif-containing nuclear protein that exhibits no detectable primary sequence homology to karyopherin α, as a novel, selective NLS-binding protein. CTNNBL1 (a si...
متن کاملCrystallographic Analysis of the Recognition of a Nuclear Localization Signal by the Nuclear Import Factor Karyopherin α
Selective nuclear import is mediated by nuclear localization signals (NLSs) and cognate transport factors known as karyopherins or importins. Karyopherin alpha recognizes "classical" monopartite and bipartite NLSs. We report the crystal structure of a 50 kDa fragment of the 60 kDa yeast karyopherin alpha, in the absence and presence of a monopartite NLS peptide at 2.2 A and 2.8 A resolution, re...
متن کاملEvidence for an evolutionary relationship between the large adaptor nucleoporin Nup192 and karyopherins.
Nucleocytoplasmic transport is facilitated by nuclear pore complexes (NPCs), which are massive proteinaceous transport channels embedded in the nuclear envelope. Nup192 is a major component of an adaptor nucleoporin subcomplex proposed to link the NPC coat with the central transport channel. Here, we present the structure of the ∼110-kDa N-terminal domain (NTD) of Nup192 at 2.7-Å resolution. Th...
متن کاملMutational Pressure Drives Evolution of Synonymous Codon Usage in Genetically Distinct Oenothera plastomes
Background: Most of the amino acids are encoded by more than one codon, termed as synonymous codons. Synonymous codon usage is not random as it is unique to species. In each amino acid family, some synonymous codons are preferred and this is referred to as synonymous codon usage bias (SCUB). Trends associated with evolution of SCUB and factors influencing its diversification in plastomes of gen...
متن کاملNuclear import of hnRNP A1 is mediated by a novel cellular cofactor related to karyopherin-beta.
Heterogeneous nuclear ribonucleoprotein A1 contains a sequence, termed M9, that functions as a potent nuclear localization signal (NLS) yet bears no similarity to the well-defined basic class of NLSs. Here, we report the identification of a novel human protein, termed MIP, that binds M9 specifically both in vivo and in vitro yet fails to interact with non-functional M9 point mutants. Of note, t...
متن کامل