6y20

From Proteopedia

Crystal structure of Protein Scalloped (222-440) bound to Protein Vestigial (298-337)

Structural highlights

6y20 is a 4 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.849Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VG_DROME Involved in determining which thoracic imaginal disk cells will form wings and halteres, perhaps by interacting with other nuclear regulatory proteins. When in combination with scalloped (sd), it acts as a transcriptional activation complex that regulates gene expression in the wing. Binding to sd switches the DNA target selectivity of sd. Required and sufficient for cell proliferation at the dorsal/ventral (D/V) boundary of the wing imaginal disk. Also required for cell proliferation in the wing imaginal disk, mediated via activation of E2f. By interacting with Dhfr, may control genes involved in DNA replication.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The most downstream elements of the Hippo pathway, the TEAD transcription factors, are regulated by several cofactors, such as Vg/VGLL1-3. Earlier findings on human VGLL1 and here on human VGLL3 show that these proteins interact with TEAD via a conserved amino acid motif called the TONDU domain. Surprisingly, our studies reveal that the TEAD-binding domain of Drosophila Vg and of human VGLL2 is more complex and contains an additional structural element, an Omega-loop, that contributes to TEAD binding. To explain this unexpected structural difference between proteins from the same family, we propose that, after the genome-wide duplications at the origin of vertebrates, the Omega-loop present in an ancestral VGLL gene has been lost in some VGLL variants. These findings illustrate how structural and functional constraints can guide the evolution of transcriptional cofactors to preserve their ability to compete with other cofactors for binding to transcription factors.

A new perspective on the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors.,Mesrouze Y, Aguilar G, Bokhovchuk F, Martin T, Delaunay C, Villard F, Meyerhofer M, Zimmermann C, Fontana P, Wille R, Vorherr T, Erdmann D, Furet P, Scheufler C, Schmelzle T, Affolter M, Chene P Sci Rep. 2020 Oct 15;10(1):17442. doi: 10.1038/s41598-020-74584-x. PMID:33060790^[5]

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

References

↑ Delanoue R, Legent K, Godefroy N, Flagiello D, Dutriaux A, Vaudin P, Becker JL, Silber J. The Drosophila wing differentiation factor vestigial-scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc. Cell Death Differ. 2004 Jan;11(1):110-22. PMID:14526388 doi:10.1038/sj.cdd.4401321
↑ Williams JA, Bell JB, Carroll SB. Control of Drosophila wing and haltere development by the nuclear vestigial gene product. Genes Dev. 1991 Dec;5(12B):2481-95. PMID:1752439 doi:10.1101/gad.5.12b.2481
↑ Simmonds AJ, Liu X, Soanes KH, Krause HM, Irvine KD, Bell JB. Molecular interactions between Vestigial and Scalloped promote wing formation in Drosophila. Genes Dev. 1998 Dec 15;12(24):3815-20. PMID:9869635
↑ Halder G, Polaczyk P, Kraus ME, Hudson A, Kim J, Laughon A, Carroll S. The Vestigial and Scalloped proteins act together to directly regulate wing-specific gene expression in Drosophila. Genes Dev. 1998 Dec 15;12(24):3900-9. PMID:9869643
↑ Mesrouze Y, Aguilar G, Bokhovchuk F, Martin T, Delaunay C, Villard F, Meyerhofer M, Zimmermann C, Fontana P, Wille R, Vorherr T, Erdmann D, Furet P, Scheufler C, Schmelzle T, Affolter M, Chène P. A new perspective on the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors. Sci Rep. 2020 Oct 15;10(1):17442. PMID:33060790 doi:10.1038/s41598-020-74584-x