3c2g | pdb_00003c2g

Crystal complex of SYS-1/POP-1 at 2.5A resolution

Structural highlights

3c2g is a 4 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	MSE
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CTNH1_CAEEL Transcription coregulator (PubMed:26073017). Part of the Wnt signaling asymmetry pathway, probably acting downstream of putative frizzled ligand mom-2, Wnt/frizzled receptors lin-17 and mom-5, and dishevelled homolog dsh-2 (PubMed:15020416, PubMed:17296929, PubMed:17567664, PubMed:19386265, PubMed:26073017). Activates or represses target gene expression, depending on upstream Wnt signals and interactions with transcription factors, such as pop-1 (PubMed:26073017, PubMed:35660370). Required for the activation of Wnt-responsive genes in the E blastomere; thereby leading to a role in endoderm specification and gut development (PubMed:17296929, PubMed:17567664). Reciprocal distribution patterns of sys-1 and pop-1/TCF in the daughters of anterior-posterior cell divisions functions in specifying cell fate; a higher sys-1 to pop-1 ratio promotes the posterior cell fate, whereas a low sys-1 to pop-1 ratio promotes the anterior fate (PubMed:17296929, PubMed:17567664). Represses expression of homeobox ttx-3 in neuroblasts of the SIAD/SIBV lineage, perhaps acting by blocking its transcriptional activation by a complex consisting of ref-2 and pop-1 (PubMed:26073017). Required for early organization of the hermaphrodite, but not the male, gonad; involved in generation of regulatory cells, known as the distal tip cells (DTC), and in formation of the somatic gonadal primordium (PubMed:11161562, PubMed:15020416, PubMed:17296929, PubMed:35196020). Involved in regulating asymmetric divisions of the somatic gonadal precursor cells (SGP), Z1 and Z4 (PubMed:15020416).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

C. elegans SYS-1 has key functional characteristics of a canonical beta-catenin, but no significant sequence similarity. Here, we report the SYS-1 crystal structure, both on its own and in a complex with POP-1, the C. elegans TCF homolog. The two structures possess signature features of canonical beta-catenin and the beta-catenin/TCF complex that could not be predicted by sequence. Most importantly, SYS-1 bears 12 armadillo repeats and the SYS-1/POP-1 interface is anchored by a conserved salt-bridge, the "charged button." We also modeled structures for three other C. elegans beta-catenins to predict the molecular basis of their distinct binding properties. Finally, we generated a phylogenetic tree, using the region of highest structural similarity between SYS-1 and beta-catenin, and found that SYS-1 clusters robustly within the beta-catenin clade. We conclude that the SYS-1 protein belongs to the beta-catenin family and suggest that additional divergent beta-catenins await discovery.

The C. elegans SYS-1 protein is a bona fide beta-catenin.,Liu J, Phillips BT, Amaya MF, Kimble J, Xu W Dev Cell. 2008 May;14(5):751-61. PMID:18477457^[9]

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

References

↑ Miskowski J, Li Y, Kimble J. The sys-1 gene and sexual dimorphism during gonadogenesis in Caenorhabditis elegans. Dev Biol. 2001 Feb 1;230(1):61-73. PMID:11161562 doi:10.1006/dbio.2000.9998
↑ Siegfried KR, Kidd AR 3rd, Chesney MA, Kimble J. The sys-1 and sys-3 genes cooperate with Wnt signaling to establish the proximal-distal axis of the Caenorhabditis elegans gonad. Genetics. 2004 Jan;166(1):171-86. PMID:15020416 doi:10.1534/genetics.166.1.171
↑ Phillips BT, Kidd AR 3rd, King R, Hardin J, Kimble J. Reciprocal asymmetry of SYS-1/beta-catenin and POP-1/TCF controls asymmetric divisions in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3231-6. PMID:17296929 doi:10.1073/pnas.0611507104
↑ Huang S, Shetty P, Robertson SM, Lin R. Binary cell fate specification during C. elegans embryogenesis driven by reiterated reciprocal asymmetry of TCF POP-1 and its coactivator beta-catenin SYS-1. Development. 2007 Jul;134(14):2685-95. PMID:17567664 doi:10.1242/dev.008268
↑ Bertrand V, Hobert O. Linking asymmetric cell division to the terminal differentiation program of postmitotic neurons in C. elegans. Dev Cell. 2009 Apr;16(4):563-75. PMID:19386265 doi:10.1016/j.devcel.2009.02.011
↑ Murgan S, Kari W, Rothbächer U, Iché-Torres M, Mélénec P, Hobert O, Bertrand V. Atypical Transcriptional Activation by TCF via a Zic Transcription Factor in C. elegans Neuronal Precursors. Dev Cell. 2015 Jun 22;33(6):737-45. PMID:26073017 doi:10.1016/j.devcel.2015.04.018
↑ Thompson JW, Michel MFV, Phillips BT. Centrosomal enrichment and proteasomal degradation of SYS-1/β-catenin requires the microtubule motor dynein. Mol Biol Cell. 2022 May 1;33(5):ar42. PMID:35196020 doi:10.1091/mbc.E22-02-0031
↑ Rumley JD, Preston EA, Cook D, Peng FL, Zacharias AL, Wu L, Jileaeva I, Murray JI. pop-1/TCF, ref-2/ZIC and T-box factors regulate the development of anterior cells in the C. elegans embryo. Dev Biol. 2022 Sep;489:34-46. PMID:35660370 doi:10.1016/j.ydbio.2022.05.019
↑ Liu J, Phillips BT, Amaya MF, Kimble J, Xu W. The C. elegans SYS-1 protein is a bona fide beta-catenin. Dev Cell. 2008 May;14(5):751-61. PMID:18477457 doi:https://dx.doi.org/S1534-5807(08)00109-3

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[1] Miskowski J, Li Y, Kimble J. The sys-1 gene and sexual dimorphism during gonadogenesis in Caenorhabditis elegans. Dev Biol. 2001 Feb 1;230(1):61-73. PMID:11161562 doi:10.1006/dbio.2000.9998

[2] Siegfried KR, Kidd AR 3rd, Chesney MA, Kimble J. The sys-1 and sys-3 genes cooperate with Wnt signaling to establish the proximal-distal axis of the Caenorhabditis elegans gonad. Genetics. 2004 Jan;166(1):171-86. PMID:15020416 doi:10.1534/genetics.166.1.171

[3] Phillips BT, Kidd AR 3rd, King R, Hardin J, Kimble J. Reciprocal asymmetry of SYS-1/beta-catenin and POP-1/TCF controls asymmetric divisions in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3231-6. PMID:17296929 doi:10.1073/pnas.0611507104

[4] Huang S, Shetty P, Robertson SM, Lin R. Binary cell fate specification during C. elegans embryogenesis driven by reiterated reciprocal asymmetry of TCF POP-1 and its coactivator beta-catenin SYS-1. Development. 2007 Jul;134(14):2685-95. PMID:17567664 doi:10.1242/dev.008268

[5] Bertrand V, Hobert O. Linking asymmetric cell division to the terminal differentiation program of postmitotic neurons in C. elegans. Dev Cell. 2009 Apr;16(4):563-75. PMID:19386265 doi:10.1016/j.devcel.2009.02.011

[6] Murgan S, Kari W, Rothbächer U, Iché-Torres M, Mélénec P, Hobert O, Bertrand V. Atypical Transcriptional Activation by TCF via a Zic Transcription Factor in C. elegans Neuronal Precursors. Dev Cell. 2015 Jun 22;33(6):737-45. PMID:26073017 doi:10.1016/j.devcel.2015.04.018

[7] Thompson JW, Michel MFV, Phillips BT. Centrosomal enrichment and proteasomal degradation of SYS-1/β-catenin requires the microtubule motor dynein. Mol Biol Cell. 2022 May 1;33(5):ar42. PMID:35196020 doi:10.1091/mbc.E22-02-0031

[8] Rumley JD, Preston EA, Cook D, Peng FL, Zacharias AL, Wu L, Jileaeva I, Murray JI. pop-1/TCF, ref-2/ZIC and T-box factors regulate the development of anterior cells in the C. elegans embryo. Dev Biol. 2022 Sep;489:34-46. PMID:35660370 doi:10.1016/j.ydbio.2022.05.019

[9] Liu J, Phillips BT, Amaya MF, Kimble J, Xu W. The C. elegans SYS-1 protein is a bona fide beta-catenin. Dev Cell. 2008 May;14(5):751-61. PMID:18477457 doi:https://dx.doi.org/S1534-5807(08)00109-3

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3c2g | pdb_00003c2g

Crystal complex of SYS-1/POP-1 at 2.5A resolution

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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