3zke: Difference between revisions

Latest revision as of 10:40, 9 May 2024

Structure of LC8 in complex with Nek9 peptide

Structural highlights

3zke is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DYL1_HUMAN Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures.^[1] ^[2] ^[3] ^[4] Binds and inhibits the catalytic activity of neuronal nitric oxide synthase.^[5] ^[6] ^[7] ^[8] Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1.^[9] ^[10] ^[11] ^[12] Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity.^[13] ^[14] ^[15] ^[16]

Publication Abstract from PubMed

The NIMA-family protein kinases Nek9/Nercc1, Nek6 and Nek7 constitute a signaling module activated in early mitosis involved in the control of spindle organization. DYNLL/LC8 (dynein light chain 8) was originally described as a component of the dynein complex, but the recent discovery of multiple interaction partners for LC8 has suggested that it has a general role as a dimerization hub that organizes different protein partners. Recent experiments suggested that LC8 binding to Nek9 was regulated by Nek9 autophosphorylation on Ser944, a residue immediately located N-terminal to the LC8 conserved (K/R)xTQT binding motif, and that this was crucial for the control of signal transduction through the Nek/Nek6/7 module. In the present work we present two crystal structures of LC8 with a peptide corresponding to the Nek9 binding region with and without a phosphorylation on Ser944. Structural analysis of LC8 with both Nek9 peptides, together with different biophysical experiments, explains the observed diminished binding affinity of Nek9 to LC8 upon phosphorylation on Ser944 within the Nek9 sequence, thus shedding light into a novel phosphorylation regulatory mechanism that interferes with LC8 protein-protein complex formation.

Structural analysis of the regulation of the DYNLL/LC8 binding to Nek9 by phosphorylation.,Gallego P, Velazquez-Campoy A, Regue L, Roig J, Reverter D J Biol Chem. 2013 Mar 12. PMID:23482567^[17]

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

References

↑ Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631
↑ Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022
↑ Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417
↑ Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200
↑ Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631
↑ Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022
↑ Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417
↑ Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200
↑ Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631
↑ Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022
↑ Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417
↑ Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200
↑ Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631
↑ Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022
↑ Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417
↑ Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200
↑ Gallego P, Velazquez-Campoy A, Regue L, Roig J, Reverter D. Structural analysis of the regulation of the DYNLL/LC8 binding to Nek9 by phosphorylation. J Biol Chem. 2013 Mar 12. PMID:23482567 doi:10.1074/jbc.M113.459149

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631

[2] Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022

[3] Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417

[4] Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200

[5] Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631

[6] Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022

[7] Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417

[8] Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200

[9] Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631

[10] Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022

[11] Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417

[12] Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200

[13] Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631

[14] Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022

[15] Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417

[16] Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200

[17] Gallego P, Velazquez-Campoy A, Regue L, Roig J, Reverter D. Structural analysis of the regulation of the DYNLL/LC8 binding to Nek9 by phosphorylation. J Biol Chem. 2013 Mar 12. PMID:23482567 doi:10.1074/jbc.M113.459149

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[3]

[4]

[5]

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@@ Line 3: / Line 3: @@
 <StructureSection load='3zke' size='340' side='right'caption='[[3zke]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3zke]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZKE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3zke]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZKE FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3zkf|3zkf]]</div></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]] 2.2&#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=3zke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zke OCA], [https://pdbe.org/3zke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zke RCSB], [https://www.ebi.ac.uk/pdbsum/3zke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zke ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/DYL1_HUMAN DYL1_HUMAN]] Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>   Binds and inhibits the catalytic activity of neuronal nitric oxide synthase.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>   Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>   Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>
+[https://www.uniprot.org/uniprot/DYL1_HUMAN DYL1_HUMAN] Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>   Binds and inhibits the catalytic activity of neuronal nitric oxide synthase.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>   Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>   Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Gallego, P]]
+[[Category: Gallego P]]
-[[Category: Regue, L]]
+[[Category: Regue L]]
-[[Category: Reverter, D]]
+[[Category: Reverter D]]
-[[Category: Roig, J]]
+[[Category: Roig J]]
-[[Category: Velazquez-Campoy, A]]
+[[Category: Velazquez-Campoy A]]
-[[Category: Contractile protein-peptide complex]]

3zke: Difference between revisions

Latest revision as of 10:40, 9 May 2024

Structure of LC8 in complex with Nek9 peptide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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