3c2g
Crystal complex of SYS-1/POP-1 at 2.5A resolution
Structural highlights
FunctionCTNH1_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 PubMedC. 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
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