Structure and molecular organization of mammalian fatty acid synthase
Structure and molecular organization of mammalian fatty acid synthase
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DOI：
10.1038/nsmb899
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发表时间：
2005-03-01
影响因子：
16.8
通讯作者：
Smith, S
中科院分区：
文献类型：
--
作者：
Asturias, FJ;Chadick, JZ;Smith, S
在动物细胞的胞质溶胶中，脂肪酸的从头合成通过多功能的同二聚体脂肪酸合酶（FAS）进行。在限制构象变异性的条件下成像的单个FAS颗粒的冷冻-EM分析，结合N末端的金标记和FAS单体的结构分析，揭示了重叠排列的两个卷曲单体。在脂肪酸合成过程中的不同步骤相关的二聚体FAS结构的比较表明，只有有限的本地重排需要不同的功能域之间的催化相互作用。线粒体螺旋可能有助于FAS的效率，并提供了一个结构上的解释报告的活性FAS单体二聚催化非活性的合作伙伴。新的FAS结构为理解FAS和相关模块化聚酮酶的结构提供了新的范例。
De novo synthesis of fatty acids in the cytosol of animal cells is carried out by the multifunctional, homodimeric fatty acid synthase (FAS). Cryo-EM analysis of single FAS particles imaged under conditions that limit conformational variability, combined with gold labeling of the N termini and structural analysis of the FAS monomers, reveals two coiled monomers in an overlapping arrangement. Comparison of dimeric FAS structures related to different steps in the fatty acid synthesis process indicates that only limited local rearrangements are required for catalytic interaction among different functional domains. Monomer coiling probably contributes to FAS efficiency and provides a structural explanation for the reported activity of a FAS monomer dimerized to a catalytically inactive partner. The new FAS structure provides a new paradigm for understanding the architecture of FAS and the related modular polyketide synthases.