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
  • 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. [email protected].
  • 6. College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China. [email protected].
  • 7. College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China. [email protected].
  • 8. Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China. [email protected].
  • 9. Laboratory of Structural Biology, Tsinghua University, Beijing, China. [email protected].
  • # 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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