8OYL

Coiled-Coil Domain of Human STIL, Q729L Mutant

「7QXH」から置き換えられました

8OYL の概要

• エントリーDOI: 10.2210/pdb8oyl/pdb
• 関連するPDBエントリー: 4YYP 5LHW 5LHZ
• 分子名称: SCL-interrupting locus protein, SODIUM ION, CADMIUM ION, ... (5 entities in total)
• 機能のキーワード: stil, coiled coil, tetramer, antiparallel, structural protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4157.54

構造登録者

Martin, F.J.O.,Shamir, M.,Woolfson, D.N.,Friedler, A. (登録日: 2023-05-05, 公開日: 2023-10-18, 最終更新日: 2023-10-25)

主引用文献

Shamir, M.,Martin, F.J.O.,Woolfson, D.N.,Friedler, A.
Molecular Mechanism of STIL Coiled-Coil Domain Oligomerization.
Int J Mol Sci, 24:-, 2023

PubMed Abstract: Coiled-coil domains (CCDs) play key roles in regulating both healthy cellular processes and the pathogenesis of various diseases by controlling protein self-association and protein-protein interactions. Here, we probe the mechanism of oligomerization of a peptide representing the CCD of the STIL protein, a tetrameric multi-domain protein that is over-expressed in several cancers and associated with metastatic spread. STIL tetramerization is mediated both by an intrinsically disordered domain (STIL) and a structured CCD (STIL CCD). Disrupting STIL oligomerization via the CCD inhibits its activity We describe a comprehensive biophysical and structural characterization of the concentration-dependent oligomerization of STIL CCD peptide. We combine analytical ultracentrifugation, fluorescence and circular dichroism spectroscopy to probe the STIL CCD peptide assembly in solution and determine dissociation constants of both the dimerization, (K = 8 ± 2 µM) and tetramerization (K = 68 ± 2 µM) of the WT STIL CCD peptide. The higher-order oligomers result in increased thermal stability and cooperativity of association. We suggest that this complex oligomerization mechanism regulates the activated levels of STIL in the cell and during centriole duplication. In addition, we present X-ray crystal structures for the CCD containing destabilising (L736E) and stabilising (Q729L) mutations, which reveal dimeric and tetrameric antiparallel coiled-coil structures, respectively. Overall, this study offers a basis for understanding the structural molecular biology of the STIL protein, and how it might be targeted to discover anti-cancer reagents.

PubMed: 37834064
DOI: 10.3390/ijms241914616

実験手法

X-RAY DIFFRACTION (1.92 Å)