Biochemistry Department, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
Biochemistry Department, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
Structure. 2018 Aug 7;26(8):1127-1136.e4. doi: 10.1016/j.str.2018.05.017. Epub 2018 Jul 5.
Cysteine desulfurase plays a central role in mitochondrial iron-sulfur cluster biogenesis by generating sulfur through the conversion of L-cysteine to L-alanine and by serving as the platform for assembling other components of the biosynthetic machinery, including ISCU, frataxin, and ferredoxin. The human mitochondrial cysteine desulfurase complex consists of two copies each of NFS1, ISD11, and acyl carrier protein. We describe results from chemical crosslinking coupled with tandem mass spectrometry and small-angle X-ray scattering studies that are consistent with a closed NFS1 dimer rather than an open one for both the cysteine desulfurase-ISCU and cysteine desulfurase-ISCU-frataxin complexes. We present a structural model for the cysteine desulfurase-ISCU-frataxin complex derived from chemical crosslinking restraints in conjunction with the recent crystal structure of the cysteine desulfurase-ISCU-zinc complex and distance constraints from nuclear magnetic resonance.
半胱氨酸脱硫酶通过将 L-半胱氨酸转化为 L-丙氨酸来产生硫，并且作为组装生物合成机制其他组件（包括 ISCU、 frataxin 和铁氧还蛋白）的平台，在线粒体铁硫簇生物发生中发挥核心作用。人线粒体半胱氨酸脱硫酶复合物由两个 NFS1、ISD11 和酰基载体蛋白的拷贝组成。我们描述了化学交联与串联质谱和小角 X 射线散射研究相结合的结果，这些结果与胱氨酸脱硫酶-ISC 和胱氨酸脱硫酶-ISC-frataxin 复合物的封闭 NFS1 二聚体而不是开放二聚体一致。我们提出了一个基于胱氨酸脱硫酶-ISC-frataxin 复合物的结构模型，该模型源自化学交联约束，并结合了最近的胱氨酸脱硫酶-ISC-锌复合物的晶体结构和来自核磁共振的距离约束。
