7o3b

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the TTBK2-CEP164 complex bound to a camelid nanobody

Structural highlights

7o3b is a 6 chain structure with sequence from Camelidae mixed library and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CE164_HUMAN Senior-Loken syndrome. The disease is caused by variants affecting the gene represented in this entry.TTBK2_HUMAN Spinocerebellar ataxia type 11. The disease is caused by mutations affecting the gene represented in this entry.

Function

CE164_HUMAN Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1.^[1] ^[2] ^[3] TTBK2_HUMAN Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro.^[4] ^[5]

Publication Abstract from PubMed

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.

Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies.,Rosa E Silva I, Bino L, Johnson CM, Rutherford TJ, Neuhaus D, Andreeva A, Cajanek L, van Breugel M Structure. 2021 Sep 7. pii: S0969-2126(21)00302-6. doi:, 10.1016/j.str.2021.08.007. PMID:34499853^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Graser S, Stierhof YD, Lavoie SB, Gassner OS, Lamla S, Le Clech M, Nigg EA. Cep164, a novel centriole appendage protein required for primary cilium formation. J Cell Biol. 2007 Oct 22;179(2):321-30. PMID:17954613 doi:http://dx.doi.org/jcb.200707181
↑ Sivasubramaniam S, Sun X, Pan YR, Wang S, Lee EY. Cep164 is a mediator protein required for the maintenance of genomic stability through modulation of MDC1, RPA, and CHK1. Genes Dev. 2008 Mar 1;22(5):587-600. doi: 10.1101/gad.1627708. Epub 2008 Feb 18. PMID:18283122 doi:http://dx.doi.org/10.1101/gad.1627708
↑ Tanos BE, Yang HJ, Soni R, Wang WJ, Macaluso FP, Asara JM, Tsou MF. Centriole distal appendages promote membrane docking, leading to cilia initiation. Genes Dev. 2013 Jan 15;27(2):163-8. doi: 10.1101/gad.207043.112. PMID:23348840 doi:http://dx.doi.org/10.1101/gad.207043.112
↑ Bouskila M, Esoof N, Gay L, Fang EH, Deak M, Begley MJ, Cantley LC, Prescott A, Storey KG, Alessi DR. TTBK2 kinase substrate specificity and the impact of spinocerebellar-ataxia-causing mutations on expression, activity, localization and development. Biochem J. 2011 Jul 1;437(1):157-67. doi: 10.1042/BJ20110276. PMID:21548880 doi:http://dx.doi.org/10.1042/BJ20110276
↑ Goetz SC, Liem KF Jr, Anderson KV. The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis. Cell. 2012 Nov 9;151(4):847-858. doi: 10.1016/j.cell.2012.10.010. PMID:23141541 doi:http://dx.doi.org/10.1016/j.cell.2012.10.010
↑ Rosa E Silva I, Bino L, Johnson CM, Rutherford TJ, Neuhaus D, Andreeva A, Cajanek L, van Breugel M. Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies. Structure. 2021 Sep 7. pii: S0969-2126(21)00302-6. doi:, 10.1016/j.str.2021.08.007. PMID:34499853 doi:http://dx.doi.org/10.1016/j.str.2021.08.007

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7o3b"

Categories: Camelidae mixed library | Homo sapiens | Large Structures | E Silva IR | Van Breugel M

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7o3b]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelidae_mixed_library Camelidae mixed library] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O3B FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7o3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o3b OCA], [https://pdbe.org/7o3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o3b RCSB], [https://www.ebi.ac.uk/pdbsum/7o3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o3b ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7o3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o3b OCA], [https://pdbe.org/7o3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o3b RCSB], [https://www.ebi.ac.uk/pdbsum/7o3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o3b ProSAT]</span></td></tr>
 </table>
 == Disease ==

7o3b

From Proteopedia

Current revision

Crystal structure of the TTBK2-CEP164 complex bound to a camelid nanobody

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox