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4BL8

Crystal structure of full-length human Suppressor of fused (SUFU)

Summary for 4BL8
Entry DOI10.2210/pdb4bl8/pdb
Related4BL9 4BLA 4BLB 4BLD
Related PRD IDPRD_900001
DescriptorMALTOSE-BINDING PERIPLASMIC PROTEIN, SUPPRESSOR OF FUSED HOMOLOG, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose (2 entities in total)
Functional Keywordssignaling protein, sugar binding protein-signaling protein complex, chimera, fusion, hedgehog gene regulation, signal transduction, gli, transcription factor
Biological sourceESCHERICHIA COLI
More
Total number of polymer chains2
Total formula weight185668.94
Authors
Karlstrom, M.,Finta, C.,Cherry, A.L.,Toftgard, R.,Jovine, L. (deposition date: 2013-05-02, release date: 2013-11-27, Last modification date: 2023-12-20)
Primary citationCherry, A.L.,Finta, C.,Karlstrom, M.,Jin, Q.,Schwend, T.,Astorga-Wells, J.,Zubarev, R.A.,Del Campo, M.,Criswell, A.R.,De Sanctis, D.,Jovine, L.,Toftgard, R.
Structural Basis of Sufu-GLI Interaction in Hedgehog Signalling Regulation
Acta Crystallogr.,Sect.D, 69:2579-, 2013
Cited by
PubMed Abstract: 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.
PubMed: 24311597
DOI: 10.1107/S0907444913028473
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3.04 Å)
Structure validation

229183

數據於2024-12-18公開中

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