9VQL

Cryo-EM structure of the dimeric Elapor1 mutant

9VQL の概要

• エントリーDOI: 10.2210/pdb9vql/pdb
• EMDBエントリー: 65259
• 分子名称: Endosome/lysosome-associated apoptosis and autophagy regulator 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: tethering factor, membrane protein
• 由来する生物種: Mus musculus (mice)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 223883.70

構造登録者

Ma, J.,Zheng, S. (登録日: 2025-07-05, 公開日: 2025-07-23, 最終更新日: 2025-08-13)

主引用文献

Shao, T.,Ma, J.,Tan, X.,Shan, H.,Xu, D.,Zhang, K.,Zheng, S.,Wang, F.
ELAPOR1 is a copper-dependent tethering factor driving proacrosomal vesicle fusion during acrosome biogenesis.
Proc.Natl.Acad.Sci.USA, 122:e2501302122-e2501302122, 2025

PubMed Abstract: The acrosome is a crucial organelle essential for sperm function and male fertility. During acrosome biogenesis, numerous proacrosomal vesicles (PAVs) are transported to the concave region of the nuclear membrane and fuse to form the acrosome. However, the mechanisms governing the fusion of PAVs to form the acrosome remain poorly understood. Here, we identify endosome-lysosome associated apoptosis and autophagy regulator 1 (ELAPOR1), a conserved protein, as a key factor in PAVs fusion during acrosome biogenesis. Male mice lacking () are infertile, exhibiting defective acrosome biogenesis and a globozoospermia-like phenotype. Using cryo-electron microscopy revealed that ELAPOR1 forms a square planar homodimer in cis, which assembles into a trans-tetramer via head-to-head homophilic interactions dependent on copper chelation. Notably, ELAPOR1 exhibits dual membrane orientation, with a predicted N - C topology and a noncanonical N - C topology in vesicles. The noncanonical N - C topology enables ELAPOR1 to function as a tethering factor bridging vesicles through head-to-head homophilic interactions. A mutant ELAPOR1 (ELAPOR1) incapable of copper chelation forms cis homodimers but fails to mediate homophilic interactions in vitro, leading to defective PAVs fusion in mice, phenocopying the -deficient mice. Additionally, ELAPOR1 was shown to interact with soluble N-ethylmaleimide sensitive factor attachment protein receptors protein STX12. Conditional knockout of in germ cells resulted in similar defects in acrosome biogenesis. Collectively, our findings suggest that ELAPOR1 functions as a tethering factor that regulates PAV fusion through a copper-dependent mechanism.

PubMed: 40737321
DOI: 10.1073/pnas.2501302122

実験手法

ELECTRON MICROSCOPY (3.6 Å)