4BL9

Crystal structure of full-length human Suppressor of fused (SUFU) mutant lacking a regulatory subdomain (crystal form I)

4BL9 の概要

• エントリーDOI: 10.2210/pdb4bl9/pdb
• 関連するPDBエントリー: 4BL8 4BLA 4BLB 4BLD
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: MALTOSE-BINDING PERIPLASMIC PROTEIN, SUPPRESSOR OF FUSED HOMOLOG, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose (2 entities in total)
• 機能のキーワード: signaling protein, sugar binding protein-signaling protein complex, hedgehog gene regulation, signal transduction, gli, transcription factor, chimera, fusion
• 由来する生物種: ESCHERICHIA COLI; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 337588.12

構造登録者

Cherry, A.L.,Finta, C.,Karlstrom, M.,Toftgard, R.,Jovine, L. (登録日: 2013-05-02, 公開日: 2013-11-27, 最終更新日: 2023-12-20)

主引用文献

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

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

実験手法

X-RAY DIFFRACTION (2.8 Å)