Structural and mutational analysis reveals that CTNNBL1 binds NLSs in a manner distinct from that of its closest armadillo-relative, karyopherin α

Karuna Ganesh; Febe Van Maldegem; Stephanie B. Telerman; Paul Simpson; Christopher M. Johnson; Roger L. Williams; Michael S. Neuberger; Cristina Rada

doi:https://doi.org/10.1016/j.febslet.2013.11.013

Structural and mutational analysis reveals that CTNNBL1 binds NLSs in a manner distinct from that of its closest armadillo-relative, karyopherin α

Karuna Ganesh, Febe Van Maldegem, Stephanie B. Telerman, Paul Simpson, Christopher M. Johnson, Roger L. Williams, Michael S. Neuberger, Cristina Rada

Research output: Contribution to journal › Article › Academic › peer-review

5 Citations (Scopus)

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.

Original language	English
Pages (from-to)	21-27
Number of pages	7
Journal	FEBS letters
Volume	588
Issue number	1
DOIs	https://doi.org/10.1016/j.febslet.2013.11.013
Publication status	Published - 3 Jan 2014
Externally published	Yes

Keywords

Armadillo domain
Nuclear import
Splicing

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@article{42e0a8fbcd5e4e10af9f82abf97d5d35,

title = "Structural and mutational analysis reveals that CTNNBL1 binds NLSs in a manner distinct from that of its closest armadillo-relative, karyopherin α",

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.",

keywords = "Armadillo domain, Nuclear import, Splicing",

author = "Karuna Ganesh and {Van Maldegem}, Febe and Telerman, {Stephanie B.} and Paul Simpson and Johnson, {Christopher M.} and Williams, {Roger L.} and Neuberger, {Michael S.} and Cristina Rada",

note = "Funding Information: Thanks to Alan Warren and Anita Chandra for advice and discussions and to the staff scientist at DSL beamlines I02 and I04-1 for their help. We are grateful for the support from the Leukaemia & Lymphoma Research to F.v.M. and Lucy Cavendish College, Cambridge to S.B.T. This work was supported by the Medical Research Council [MRC reference number MC_U105178806 ].",

year = "2014",

month = jan,

day = "3",

doi = "https://doi.org/10.1016/j.febslet.2013.11.013",

language = "English",

volume = "588",

pages = "21--27",

journal = "FEBS letters",

issn = "0014-5793",

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number = "1",

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TY - JOUR

T1 - Structural and mutational analysis reveals that CTNNBL1 binds NLSs in a manner distinct from that of its closest armadillo-relative, karyopherin α

AU - Ganesh, Karuna

AU - Van Maldegem, Febe

AU - Telerman, Stephanie B.

AU - Simpson, Paul

AU - Johnson, Christopher M.

AU - Williams, Roger L.

AU - Neuberger, Michael S.

AU - Rada, Cristina

N1 - Funding Information: Thanks to Alan Warren and Anita Chandra for advice and discussions and to the staff scientist at DSL beamlines I02 and I04-1 for their help. We are grateful for the support from the Leukaemia & Lymphoma Research to F.v.M. and Lucy Cavendish College, Cambridge to S.B.T. This work was supported by the Medical Research Council [MRC reference number MC_U105178806 ].

PY - 2014/1/3

Y1 - 2014/1/3

N2 - 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.

AB - 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.

KW - Armadillo domain

KW - Nuclear import

KW - Splicing

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U2 - https://doi.org/10.1016/j.febslet.2013.11.013

DO - https://doi.org/10.1016/j.febslet.2013.11.013

M3 - Article

C2 - 24269683

SN - 0014-5793

VL - 588

SP - 21

EP - 27

JO - FEBS letters

JF - FEBS letters

IS - 1

ER -

Structural and mutational analysis reveals that CTNNBL1 binds NLSs in a manner distinct from that of its closest armadillo-relative, karyopherin α

Abstract

Keywords

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