4BLA
Crystal structure of full-length human Suppressor of fused (SUFU) mutant lacking a regulatory subdomain (crystal form II)
Summary for 4BLA
Entry DOI | 10.2210/pdb4bla/pdb |
Related | 4BL8 4BL9 4BLB 4BLD |
Descriptor | MALTOSE-BINDING PERIPLASMIC PROTEIN, SUPPRESSOR OF FUSED HOMOLOG (1 entity in total) |
Functional Keywords | signaling protein, sugar binding protein-signaling protein complex, hedgehog gene regulation, signal transduction, gli, transcription factor |
Biological source | ESCHERICHIA COLI More |
Total number of polymer chains | 4 |
Total formula weight | 336218.94 |
Authors | Cherry, A.L.,Finta, C.,Karlstrom, M.,Toftgard, R.,Jovine, L. (deposition date: 2013-05-02, release date: 2013-11-27, Last modification date: 2023-12-20) |
Primary citation | Cherry, 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: 24311597DOI: 10.1107/S0907444913028473 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (3.5 Å) |
Structure validation
Download full validation report