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-Structure paper
| タイトル | Structural dynamics of human fatty acid synthase in the condensing cycle. |
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| ジャーナル・号・ページ | Nature, Vol. 641, Issue 8062, Page 529-536, Year 2025 |
| 掲載日 | 2025年2月20日 |
著者 | Wooyoung Choi / Chengmin Li / Yifei Chen / YongQiang Wang / Yifan Cheng / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nature / PubMed:39978408 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2 - 3.3 Å |
| 構造データ | ![]() EMDB-44230: Human endogenous FASN alone - Class 1" to "Human endogenous FASN alone - Class 1 composite map ![]() EMDB-44231: Human endogenous FASN alone - Class 1 consensus map ![]() EMDB-44263: Human endogenous FASN alone - Class 1 focused modifying wing ![]() EMDB-44264: Human endogenous FASN alone - Class 1 focused condensing wing ![]() EMDB-44267: Human endogenous FASN with Orlistat - composite map ![]() EMDB-44268: Human endogenous FASN with Orlistat - consensus map ![]() EMDB-44269: Human endogenous FASN with Orlistat - focused modifying wing ![]() EMDB-44270: Human endogenous FASN with Orlistat - focused condensing wing ![]() EMDB-44295: Human endogenous FASN with 1,3-DBP - Class 2 composite map ![]() EMDB-44296: Human endogenous FASN with 1,3-DBP - Class 2 consensus map ![]() EMDB-44297: Human endogenous FASN with 1,3-DPB - Class 2 focused modifying wing ![]() EMDB-44298: Human endogenous FASN with 1,3-DBP - Class 2 focused condensing wing ![]() EMDB-44300: Human endogenous FASN with 1,3-DBP - Class 1 composite map ![]() EMDB-44301: Human endogenous FASN with 1,3-DBP - Class 1 consensus map EMDB-44329, PDB-9b7z: EMDB-44330, PDB-9b80: ![]() EMDB-44371: Human endogenous FASN - combined class1 modifying wing with classification EMDB-44378: Human endogenous FASN - combined class1 condensing wing with classification |
| 由来 |
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キーワード | BIOSYNTHETIC PROTEIN / De novo fatty acid synthesis Fatty acid synthase / TRANSFERASE |
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homo sapiens (ヒト)
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