| Structural highlights
Function
[MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. [GLI1_HUMAN] Acts as a transcriptional activator. May regulate the transcription of specific genes during normal development. May play a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling and thus cell proliferation and differentiation.[1] [2]
Publication Abstract from PubMed
Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU-GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU-GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics.
Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation.,Cherry AL, Finta C, Karlstrom M, Jin Q, Schwend T, Astorga-Wells J, Zubarev RA, Del Campo M, Criswell AR, de Sanctis D, Jovine L, Toftgard R Acta Crystallogr D Biol Crystallogr. 2013 Dec;69(Pt 12):2563-79. doi:, 10.1107/S0907444913028473. Epub 2013 Nov 19. PMID:24311597[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Murone M, Luoh SM, Stone D, Li W, Gurney A, Armanini M, Grey C, Rosenthal A, de Sauvage FJ. Gli regulation by the opposing activities of fused and suppressor of fused. Nat Cell Biol. 2000 May;2(5):310-2. PMID:10806483 doi:10.1038/35010610
- ↑ Koyabu Y, Nakata K, Mizugishi K, Aruga J, Mikoshiba K. Physical and functional interactions between Zic and Gli proteins. J Biol Chem. 2001 Mar 9;276(10):6889-92. Epub 2001 Jan 12. PMID:11238441 doi:http://dx.doi.org/10.1074/jbc.C000773200
- ↑ Cherry AL, Finta C, Karlstrom M, Jin Q, Schwend T, Astorga-Wells J, Zubarev RA, Del Campo M, Criswell AR, de Sanctis D, Jovine L, Toftgard R. Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation. Acta Crystallogr D Biol Crystallogr. 2013 Dec;69(Pt 12):2563-79. doi:, 10.1107/S0907444913028473. Epub 2013 Nov 19. PMID:24311597 doi:http://dx.doi.org/10.1107/S0907444913028473
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