National Natural Science Foundation of China (NSFC)
32201033
中国
National Natural Science Foundation of China (NSFC)
32171259
中国
National Key Research and Development Program of China
2022YFA1305900
中国
Shanghai Rising-Star Program
23QA1406400
中国
引用
ジャーナル: Commun Biol / 年: 2024 タイトル: The structural and functional analysis of mycobacteria cysteine desulfurase-loaded encapsulin. 著者: Yanting Tang / Yanyan Liu / Mingjing Zhang / Weiqi Lan / Mengyuan Ma / Cheng Chen / Saibin Wu / Rong Chen / Yiran Yan / Lu Feng / Ying Li / Luke W Guddat / Yan Gao / Xiang Liu / Zihe Rao / 要旨: Encapsulin nanocompartments loaded with dedicated cargo proteins via unique targeting peptides, play a key role in stress resistance, iron storage and natural product biosynthesis. Mmp1 and cysteine ...Encapsulin nanocompartments loaded with dedicated cargo proteins via unique targeting peptides, play a key role in stress resistance, iron storage and natural product biosynthesis. Mmp1 and cysteine desulfurase (Enc-CD) have been identified as the most abundant representatives of family 2 encapsulin systems. However, the molecular assembly, catalytic mechanism, and physiological functions of the Mmp1 encapsulin system have not been studied in detail. Here we isolate and characterize an Enc-CD-loaded Mmp1 encapsulin system from Mycobacterium smegmatis mc155. The cryo-EM structure of the Mmp1 encapsulin and the crystal structure of the naked cargo Enc-CD have been determined. The structure shows that the Mmp1 protomer assembles two conformation models, the icosahedron (T = 1) and homodecamer, with the resolution of 2.60 Å and 2.69 Å. The Enc-CD at 2.10 Å resolution is dimeric and loaded into the Mmp1 (T = 1) encapsulin through the N-terminal long disordered region. Mmp1 encapsulin protects Enc-CD against oxidation as well as to maintain structural stability. These studies provide new insights into the mechanism by which Enc-CD-loaded encapsulin stores sulfur and provides a framework for discovery of new anti-mycobacterial therapeutics.