Insights into pyrrolysine function from structures of a trimethylamine methyltransferase and its corrinoid protein complex.

Insights into pyrrolysine function from structures of a trimethylamine methyltransferase and its corrinoid protein complex.
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DOI:
10.1038/s42003-022-04397-3
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发表时间:
2023-01-16
影响因子:
5.9
通讯作者:
--
中科院分区:
生物学2区
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--
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第22个基因编码的氨基酸吡咯赖氨酸在甲烷菌在单-、二-和三-甲胺上生长的关键步骤中起着独特的作用,通过激活这些底物的甲基转移到类咕啉辅因子。先前的巴克尔甲烷八叠球菌单甲胺甲基转移酶的晶体结构阐明了吡咯赖氨酸的结构,并提供了对其在单甲胺活化中的作用的深入了解。在此,我们报告了一个含吡咯赖氨酸的蛋白质的第二个结构,M。巴克尔氏三甲基胺甲基转移酶MttB,其结构与亚硫酸盐结合,亚硫酸盐是三甲基胺的底物类似物。我们还报告了MttB与其同源类咕啉蛋白MttC复合的结构,MttC在产甲烷过程中特异性地接收来自吡咯赖氨酸激活的三甲胺底物的甲基。这些结构一起提供了关键的见解吡咯赖氨酸在甲基转移中的作用,从三甲基胺的corrinoid辅因子在MttC。巴氏甲烷八叠球菌三甲基胺甲基转移酶(MttB)及其底物的结构揭示了吡咯赖氨酸在MttC中甲基从三甲基胺转移到类咕啉辅因子中的作用。
The 22nd genetically encoded amino acid, pyrrolysine, plays a unique role in the key step in the growth of methanogens on mono-, di-, and tri-methylamines by activating the methyl group of these substrates for transfer to a corrinoid cofactor. Previous crystal structures of the Methanosarcina barkeri monomethylamine methyltransferase elucidated the structure of pyrrolysine and provide insight into its role in monomethylamine activation. Herein, we report the second structure of a pyrrolysine-containing protein, the M. barkeri trimethylamine methyltransferase MttB, and its structure bound to sulfite, a substrate analog of trimethylamine. We also report the structure of MttB in complex with its cognate corrinoid protein MttC, which specifically receives the methyl group from the pyrrolysine-activated trimethylamine substrate during methanogenesis. Together these structures provide key insights into the role of pyrrolysine in methyl group transfer from trimethylamine to the corrinoid cofactor in MttC. Structures of Methanosarcina barkeri trimethylamine methyltransferase (MttB) with its substrates reveal the role of pyrrolysine in methyl group transfer from trimethylamine to the corrinoid cofactor in MttC.
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