22ib | pdb_000022ib

CryoEM structure of Human LonP1-TFAM complex

spinqualitylabelsall models 22ib, resolution 3.22Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 22ib is a 7 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.22Å Ligands: ADP, AGS, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LONM_HUMAN ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner. May regulate mitochondrial DNA replication and/or gene expression using site-specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters. Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein.[HAMAP-Rule:MF_03120] Publication Abstract from PubMed The human mitochondrial Lon protease (LonP1) is a central regulator of mitochondrial DNA copy number and metabolic reprogramming. However, the structural basis for how LonP1 recognizes native physiological substrates remains elusive. Here, we present the high-resolution cryo-EM structure of the human LonP1 hexamer actively engaging its native substrate, TFAM. The reconstruction reveals a distinct bipartite search-and-shred mechanism. Unlike its bacterial homologs, the human N-terminal domain (NTD) adopts a compact architecture acting as a selective vestibule to recruit and initially unfold the substrate tertiary structure. Subsequently, the polypeptide is threaded through the central channel via a hand-over-hand mechanism driven by a spiral array of aromatic pore-loops. This structural framework provides a mechanistic rationale for the spatial segregation of LonP1 and offers a template for targeting mitochondrial proteostasis in human diseases. Structural Analysis of Human LonP1 Protease Bound with the Native Substrate.,Li M, Liu H, Zhang S, Gao Q, Li S, Wang J, Zhang K Life (Basel). 2026 Mar 16;16(3):478. doi: 10.3390/life16030478. PMID:41900996 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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