-
Something wrong with this record ?
Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies
I. Rosa E Silva, L. Binó, CM. Johnson, TJ. Rutherford, D. Neuhaus, A. Andreeva, L. Čajánek, M. van Breugel
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
MC_U105178934
Medical Research Council - United Kingdom
MC_U105184326
Medical Research Council - United Kingdom
MC_UP_1201/3
Medical Research Council - United Kingdom
NLK
Cell Press Free Archives
from 1995-01-01 to 1 year ago
Free Medical Journals
from 1995 to 1 year ago
Free Medical Journals
from 1995 to 1 year ago
- MeSH
- Ciliopathies genetics MeSH
- Circular Dichroism MeSH
- HEK293 Cells MeSH
- Protein Conformation MeSH
- Humans MeSH
- Microtubule Proteins chemistry genetics metabolism MeSH
- Models, Molecular MeSH
- Mutation * MeSH
- Protein Serine-Threonine Kinases chemistry metabolism MeSH
- Protein Domains MeSH
- Microtubule-Associated Proteins metabolism MeSH
- Protein Stability MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Cilia formation is essential for human life. One of the earliest events in the ciliogenesis program is the recruitment of tau-tubulin kinase 2 (TTBK2) by the centriole distal appendage component CEP164. Due to the lack of high-resolution structural information on this complex, it is unclear how it is affected in human ciliopathies such as nephronophthisis. Furthermore, it is poorly understood if binding to CEP164 influences TTBK2 activities. Here, we present a detailed biochemical, structural, and functional analysis of the CEP164-TTBK2 complex and demonstrate how it is compromised by two ciliopathic mutations in CEP164. Moreover, we also provide insights into how binding to CEP164 is coordinated with TTBK2 activities. Together, our data deepen our understanding of a crucial step in cilia formation and will inform future studies aimed at restoring CEP164 functionality in a debilitating human ciliopathy.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc22011381
- 003
- CZ-PrNML
- 005
- 20241217085116.0
- 007
- ta
- 008
- 220425s2022 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.str.2021.08.007 $2 doi
- 035 __
- $a (PubMed)34499853
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Rosa E Silva, Ivan $u Queen Mary University of London, School of Biological and Chemical Sciences, 2 Newark Street, London E1 2AT, UK; Medical Research Council - Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: ivan.silva@alumni.usp.br
- 245 10
- $a Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies / $c I. Rosa E Silva, L. Binó, CM. Johnson, TJ. Rutherford, D. Neuhaus, A. Andreeva, L. Čajánek, M. van Breugel
- 520 9_
- $a Cilia formation is essential for human life. One of the earliest events in the ciliogenesis program is the recruitment of tau-tubulin kinase 2 (TTBK2) by the centriole distal appendage component CEP164. Due to the lack of high-resolution structural information on this complex, it is unclear how it is affected in human ciliopathies such as nephronophthisis. Furthermore, it is poorly understood if binding to CEP164 influences TTBK2 activities. Here, we present a detailed biochemical, structural, and functional analysis of the CEP164-TTBK2 complex and demonstrate how it is compromised by two ciliopathic mutations in CEP164. Moreover, we also provide insights into how binding to CEP164 is coordinated with TTBK2 activities. Together, our data deepen our understanding of a crucial step in cilia formation and will inform future studies aimed at restoring CEP164 functionality in a debilitating human ciliopathy.
- 650 _2
- $a vazebná místa $7 D001665
- 650 _2
- $a ciliopatie $x genetika $7 D000072661
- 650 _2
- $a cirkulární dichroismus $7 D002942
- 650 _2
- $a HEK293 buňky $7 D057809
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a mikrotubulární proteiny $x chemie $x genetika $x metabolismus $7 D008868
- 650 _2
- $a proteiny asociované s mikrotubuly $x metabolismus $7 D008869
- 650 _2
- $a molekulární modely $7 D008958
- 650 12
- $a mutace $7 D009154
- 650 _2
- $a vazba proteinů $7 D011485
- 650 _2
- $a konformace proteinů $7 D011487
- 650 _2
- $a proteinové domény $7 D000072417
- 650 _2
- $a protein-serin-threoninkinasy $x chemie $x metabolismus $7 D017346
- 650 _2
- $a stabilita proteinů $7 D055550
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Binó, Lucia $u Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno 62500, Czech Republic $7 xx0326742
- 700 1_
- $a Johnson, Christopher M $u Medical Research Council - Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
- 700 1_
- $a Rutherford, Trevor J $u Medical Research Council - Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
- 700 1_
- $a Neuhaus, David $u Medical Research Council - Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
- 700 1_
- $a Andreeva, Antonina $u Medical Research Council - Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
- 700 1_
- $a Čajánek, Lukáš $u Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno 62500, Czech Republic
- 700 1_
- $a van Breugel, Mark $u Queen Mary University of London, School of Biological and Chemical Sciences, 2 Newark Street, London E1 2AT, UK; Medical Research Council - Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: m.vanbreugel@qmul.ac.uk
- 773 0_
- $w MED00006440 $t Structure $x 1878-4186 $g Roč. 30, č. 1 (2022), s. 114-128.e9
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/34499853 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20220425 $b ABA008
- 991 __
- $a 20241217085113 $b ABA008
- 999 __
- $a ok $b bmc $g 1789123 $s 1162579
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2022 $b 30 $c 1 $d 114-128.e9 $e 20210908 $i 1878-4186 $m Structure $n Structure $x MED00006440
- GRA __
- $a MC_U105178934 $p Medical Research Council $2 United Kingdom
- GRA __
- $a MC_U105184326 $p Medical Research Council $2 United Kingdom
- GRA __
- $a MC_UP_1201/3 $p Medical Research Council $2 United Kingdom
- LZP __
- $a Pubmed-20220425
