9B80

Human endogenous FASN with 1,3-DBP - Class 1 focused modifying wing

9B80 の概要

• エントリーDOI: 10.2210/pdb9b80/pdb
• EMDBエントリー: 44300 44330 44371
• 分子名称: Fatty acid synthase (1 entity in total)
• 機能のキーワード: de novo fatty acid synthesis fatty acid synthase, biosynthetic protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 362156.62

構造登録者

Choi, W.,Li, C.,Chen, Y.,Wang, Y.,Cheng, Y. (登録日: 2024-03-28, 公開日: 2025-02-26, 最終更新日: 2025-05-21)

主引用文献

Choi, W.,Li, C.,Chen, Y.,Wang, Y.,Cheng, Y.
Structural dynamics of human fatty acid synthase in the condensing cycle.
Nature, 641:529-536, 2025

PubMed Abstract: Long-chain fatty acids are the building blocks of fat in human bodies. In mammals, fatty acid synthase (FASN) contains multiple enzymatic domains to catalyse all chemical reactions needed for de novo fatty acid synthesis. Although the chemical reactions carried out by these enzymatic domains are well defined, how the dimeric FASN with an open architecture continuously catalyses such reactions to synthesize a complete fatty acid remains elusive. Here, using a strategy of tagging and purifying endogenous FASN in HEK293T cells for single-particle cryo-electron microscopy studies, we characterized the structural dynamics of endogenous human FASN. We captured conformational snapshots of various functional substates in the condensing cycle and developed a procedure to analyse the particle distribution landscape of FASN with different orientations between its condensing and modifying wings. Together, our findings reveal that FASN function does not require a large rotational motion between its two main functional domains during the condensing cycle, and that the catalytic reactions in the condensing cycle carried out by the two monomers are unsynchronized. Our data thus provide a new composite view of FASN dynamics during the fatty acid synthesis condensing cycle.

PubMed: 39978408
DOI: 10.1038/s41586-025-08782-w

実験手法

ELECTRON MICROSCOPY (2.7 Å)