Structural characterization of KKT4, an unconventional microtubule-binding kinetochore protein.
BRCT domain
KKT4
NMR spectroscopy
Trypanosoma brucei
X-ray crystallography
coiled coil
crosslinking mass spectrometry
kinetochore
kinetoplastid
microtubules
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
02 09 2021
02 09 2021
Historique:
received:
21
10
2020
revised:
17
02
2021
accepted:
08
04
2021
pubmed:
30
4
2021
medline:
17
3
2022
entrez:
29
4
2021
Statut:
ppublish
Résumé
The kinetochore is the macromolecular machinery that drives chromosome segregation by interacting with spindle microtubules. Kinetoplastids (such as Trypanosoma brucei), a group of evolutionarily divergent eukaryotes, have a unique set of kinetochore proteins that lack any significant homology to canonical kinetochore components. To date, KKT4 is the only kinetoplastid kinetochore protein that is known to bind microtubules. Here we use X-ray crystallography, NMR spectroscopy, and crosslinking mass spectrometry to characterize the structure and dynamics of KKT4. We show that its microtubule-binding domain consists of a coiled-coil structure followed by a positively charged disordered tail. The structure of the C-terminal BRCT domain of KKT4 reveals that it is likely a phosphorylation-dependent protein-protein interaction domain. The BRCT domain interacts with the N-terminal region of the KKT4 microtubule-binding domain and with a phosphopeptide derived from KKT8. Taken together, these results provide structural insights into the unconventional kinetoplastid kinetochore protein KKT4.
Identifiants
pubmed: 33915106
pii: S0969-2126(21)00120-9
doi: 10.1016/j.str.2021.04.004
pmc: PMC8443799
pii:
doi:
Substances chimiques
Microtubule-Associated Proteins
0
Protozoan Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1014-1028.e8Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 210622/Z/18/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Structure. 2003 Nov;11(11):1453-9
pubmed: 14604535
Cold Spring Harb Perspect Biol. 2014 Jul 01;6(7):a015826
pubmed: 24984773
J Biomol NMR. 1999 Mar;13(3):289-302
pubmed: 10212987
Bioinformatics. 2019 Dec 15;35(24):5326-5327
pubmed: 31263867
EMBO J. 2006 Nov 29;25(23):5504-15
pubmed: 17093495
J Cell Biol. 2012 Mar 5;196(5):563-71
pubmed: 22371557
J Struct Biol. 2002 Jan-Feb;137(1-2):54-64
pubmed: 12064933
J Cell Biol. 2001 Dec 24;155(7):1137-45
pubmed: 11756468
Science. 1991 May 24;252(5009):1162-4
pubmed: 2031185
Science. 2003 Oct 24;302(5645):639-42
pubmed: 14576433
Proteins. 2005 Jun 1;59(4):687-96
pubmed: 15815974
J Cell Sci. 2004 Nov 1;117(Pt 23):5461-77
pubmed: 15509863
Elife. 2017 Aug 25;6:
pubmed: 28841134
Cell. 2014 Mar 13;156(6):1247-1258
pubmed: 24582333
Curr Protoc Bioinformatics. 2016 Jun 20;54:5.6.1-5.6.37
pubmed: 27322406
Essays Biochem. 2020 Sep 4;64(2):371-382
pubmed: 32502246
J Cell Biol. 2017 Feb;216(2):379-391
pubmed: 28034897
J Cell Biol. 2016 Oct 10;215(1):77-93
pubmed: 27697923
Biology (Basel). 2017 Jan 24;6(1):
pubmed: 28125021
BMC Biol. 2020 Mar 2;18(1):23
pubmed: 32122335
Methods Mol Biol. 2008;426:221-46
pubmed: 18542867
Genome Biol. 2007;8(3):R37
pubmed: 17352808
Nat Struct Mol Biol. 2004 Jun;11(6):519-25
pubmed: 15133503
Genome Biol. 2006;7(3):R23
pubmed: 16563186
Nat Methods. 2009 Sep;6(9):651-3
pubmed: 19684596
Genetics. 2013 Aug;194(4):817-46
pubmed: 23908374
J Magn Reson. 2000 Apr;143(2):423-6
pubmed: 10729271
Open Biol. 2019 Dec;9(12):190236
pubmed: 31795916
Cell. 2002 Oct 18;111(2):163-72
pubmed: 12408861
Nucleic Acids Res. 2010 Jan;38(Database issue):D457-62
pubmed: 19843604
Curr Biol. 2008 Nov 25;18(22):1778-84
pubmed: 19026543
Nat Rev Mol Cell Biol. 2008 Jan;9(1):33-46
pubmed: 18097444
Cell. 2006 Dec 1;127(5):983-97
pubmed: 17129783
Biol Lett. 2010 Jun 23;6(3):342-5
pubmed: 20031978
Nat Rev Mol Cell Biol. 2013 Jan;14(1):25-37
pubmed: 23258294
Science. 1997 Jan 31;275(5300):632-7
pubmed: 9005842
Bioinformatics. 2006 Feb 1;22(3):356-8
pubmed: 16317077
Open Biol. 2016 Mar;6(3):
pubmed: 26984294
Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515
pubmed: 30395287
Biochemistry. 1996 Apr 16;35(15):4867-77
pubmed: 8664278
J Biomol NMR. 1995 Nov;6(3):277-93
pubmed: 8520220
Protein Sci. 2006 Dec;15(12):2795-804
pubmed: 17088319
Protein Sci. 2018 Jan;27(1):112-128
pubmed: 28836357
Trends Biochem Sci. 2016 Jan;41(1):20-32
pubmed: 26654279
Nat Protoc. 2011 Mar;6(3):365-87
pubmed: 21372817
Nucleic Acids Res. 2018 Jul 2;46(W1):W200-W204
pubmed: 29905871
J Biomol NMR. 2013 Jul;56(3):227-41
pubmed: 23728592
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Cell Cycle. 2011 Aug 1;10(15):2461-70
pubmed: 21734457
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):336-43
pubmed: 22505254
Acta Crystallogr D Biol Crystallogr. 2006 Sep;62(Pt 9):1002-11
pubmed: 16929101
Nat Commun. 2019 Jul 30;10(1):3404
pubmed: 31363125
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Mol Biol Rep. 1993 Apr;17(3):167-83
pubmed: 8326953
Mol Cell. 2004 May 7;14(3):405-12
pubmed: 15125843
Science. 2005 Jul 15;309(5733):416-22
pubmed: 16020726
Bioinformatics. 2009 May 1;25(9):1189-91
pubmed: 19151095
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
Protein Sci. 2005 Sep;14(9):2421-8
pubmed: 16131665
Biomol NMR Assign. 2020 Oct;14(2):309-315
pubmed: 32696260
Biochemistry. 1989 Nov 14;28(23):8972-9
pubmed: 2690953
Dev Cell. 2012 Nov 13;23(5):968-80
pubmed: 23085020
Anal Biochem. 1996 Sep 5;240(2):155-66
pubmed: 8811899
Cell. 2008 May 2;133(3):427-39
pubmed: 18455984
Annu Rev Cell Dev Biol. 1997;13:83-117
pubmed: 9442869
EMBO J. 1998 Nov 2;17(21):6404-11
pubmed: 9799248
Nat Commun. 2016 Apr 20;7:11407
pubmed: 27095104
EMBO Rep. 2017 Sep;18(9):1559-1571
pubmed: 28642229
J Cell Sci. 2020 Apr 29;133(8):
pubmed: 32184264
Nat Commun. 2014;5:2964
pubmed: 24413531
Cold Spring Harb Perspect Biol. 2016 Sep 01;8(9):
pubmed: 27587616
J Magn Reson. 2007 Jul;187(1):163-9
pubmed: 17468025
Brief Bioinform. 2019 Jul 19;20(4):1160-1166
pubmed: 28968734
J Biomol NMR. 1997 Sep;10(2):129-42
pubmed: 9369014
Nat Struct Mol Biol. 2007 Jan;14(1):54-9
pubmed: 17195848
Proc Natl Acad Sci U S A. 2006 May 23;103(21):8060-5
pubmed: 16690741
J Biol Chem. 2006 Apr 7;281(14):9677-87
pubmed: 16436376
Science. 2003 Oct 24;302(5645):636-9
pubmed: 14576432
FEBS Lett. 1991 Nov 18;293(1-2):72-80
pubmed: 1959674
J Magn Reson. 2000 May;144(1):123-8
pubmed: 10783281
J Cell Biol. 2010 May 17;189(4):713-23
pubmed: 20479468
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Mol Cell Proteomics. 2015 Apr;14(4):1137-47
pubmed: 25648531
J Cell Biol. 2018 Nov 5;217(11):3886-3900
pubmed: 30209069
Nat Struct Mol Biol. 2004 Jun;11(6):512-8
pubmed: 15133502