2. Academic Validation
  3. The structural and functional analysis of mycobacteria cysteine desulfurase-loaded encapsulin

The structural and functional analysis of mycobacteria cysteine desulfurase-loaded encapsulin

  • Commun Biol. 2024 Dec 19;7(1):1656. doi: 10.1038/s42003-024-07299-8.
Yanting Tang # 1,  Yanyan Liu # 1,  Mingjing Zhang # 2,  Weiqi Lan 2,  Mengyuan Ma 1,  Cheng Chen 3,  Saibin Wu 1,  Rong Chen 1,  Yiran Yan 2,  Lu Feng 1,  Ying Li 1,  Luke W Guddat 4,  Yan Gao 5,  Xiang Liu 6,  Zihe Rao 7 8 9
Affiliations

Affiliations

  • 1 College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.
  • 2 Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • 3 School of Life Sciences, Tianjin University, Tianjin, China.
  • 4 School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
  • 5 Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China. gaoyan@shanghaitech.edu.cn.
  • 6 College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China. liux@nankai.edu.cn.
  • 7 College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China. raozh@tsinghua.edu.cn.
  • 8 Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China. raozh@tsinghua.edu.cn.
  • 9 Laboratory of Structural Biology, Tsinghua University, Beijing, China. raozh@tsinghua.edu.cn.
  • # Contributed equally.
PMID: 39702509 DOI: 10.1038/s42003-024-07299-8
Abstract

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 mc2155. 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.

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