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

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...

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Published in:Communications biology Vol. 7; no. 1; pp. 1656 - 14
Main Authors: Tang, Yanting, Liu, Yanyan, Zhang, Mingjing, Lan, Weiqi, Ma, Mengyuan, Chen, Cheng, Wu, Saibin, Chen, Rong, Yan, Yiran, Feng, Lu, Li, Ying, Guddat, Luke W., Gao, Yan, Liu, Xiang, Rao, Zihe
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 19.12.2024
Nature Publishing Group
Nature Portfolio
Subjects:
101/28
631/45/535
631/57
82/83
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bioengineering
Biology
Biomedical and Life Sciences
Biosynthesis
Carbon-Sulfur Lyases - chemistry
Carbon-Sulfur Lyases - metabolism
Conformation
Cryoelectron Microscopy
Crystal structure
Crystallography, X-Ray
Cysteine
Leprosy
Life Sciences
Metabolism
Models, Molecular
Mycobacterium smegmatis
Mycobacterium smegmatis - enzymology
Mycobacterium smegmatis - metabolism
Natural products
Oxidation
Peptides
Physiology
Polymerization
Protein Conformation
Proteins
Structure-function relationships
Sulfur
Therapeutic applications
ISSN:2399-3642, 2399-3642
Online Access:Get full text
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Summary: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 mc 2 155. 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. Tang et al. present the isolation and characterization of an Mmp1 encapsulin system from Mycobacterium smegmatis , highlighting its structural and functional features. The study reveals the cryo-EM and crystal structures, offering insights into the role of Enc-CD-loaded encapsulin in sulfur storage, stress resistance, and potential therapeutic applications against mycobacterial infections.
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ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-024-07299-8