5EFM

Beclin 1 Flexible-helical Domian (FHD) (141-171)

5EFM の概要

• エントリーDOI: 10.2210/pdb5efm/pdb
• 分子名称: Beclin-1, SULFATE ION (3 entities in total)
• 機能のキーワード: flexible helix, apoptosis
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm . Beclin-1-C 35 kDa: Mitochondrion . Beclin-1-C 37 kDa: Mitochondrion : Q14457
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3782.10

構造登録者

Sinha, S.,Mei, Y. (登録日: 2015-10-23, 公開日: 2016-07-20, 最終更新日: 2024-10-16)

主引用文献

Mei, Y.,Ramanathan, A.,Glover, K.,Stanley, C.,Sanishvili, R.,Chakravarthy, S.,Yang, Z.,Colbert, C.L.,Sinha, S.C.
Conformational Flexibility Enables the Function of a BECN1 Region Essential for Starvation-Mediated Autophagy.
Biochemistry, 55:1945-1958, 2016

PubMed Abstract: BECN1 is essential for autophagy, a critical eukaryotic cellular homeostasis pathway. Here we delineate a highly conserved BECN1 domain located between previously characterized BH3 and coiled-coil domains and elucidate its structure and role in autophagy. The 2.0 Å sulfur-single-wavelength anomalous dispersion X-ray crystal structure of this domain demonstrates that its N-terminal half is unstructured while its C-terminal half is helical; hence, we name it the flexible helical domain (FHD). Circular dichroism spectroscopy, double electron-electron resonance-electron paramagnetic resonance, and small-angle X-ray scattering (SAXS) analyses confirm that the FHD is partially disordered, even in the context of adjacent BECN1 domains. Molecular dynamic simulations fitted to SAXS data indicate that the FHD transiently samples more helical conformations. FHD helicity increases in 2,2,2-trifluoroethanol, suggesting it may become more helical upon binding. Lastly, cellular studies show that conserved FHD residues are required for starvation-induced autophagy. Thus, the FHD likely undergoes a binding-associated disorder-to-helix transition, and conserved residues critical for this interaction are essential for starvation-induced autophagy.

PubMed: 26937551
DOI: 10.1021/acs.biochem.5b01264

実験手法

X-RAY DIFFRACTION (1.95 Å)