8u39

Structure of Human Mitochondrial Chaperonin V72I mutant

spinqualitylabelsall models 8u39, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8u39 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 3.4Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CH60_HUMAN Autosomal dominant spastic paraplegia type 13;Pelizaeus-Merzbacher-like disease due to HSPD1 mutation. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function CH60_HUMAN Implicated in mitochondrial protein import and macromolecular assembly. May facilitate the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. Publication Abstract from PubMed Chaperonins Hsp60s are required for cellular vitality by assisting protein folding in an ATP-dependent mechanism. Although conserved, the human mitochondrial mHsp60 exhibits molecular characteristics distinct from the E. coli GroEL, with different conformational assembly and higher subunit association dynamics, suggesting a different mechanism. We previously found that the pathological mutant mHsp60(V72I) exhibits enhanced subunit association stability and ATPase activity. To provide structural explanations for the V72I mutational effects, here we determined a cryo-EM structure of mHsp60(V72I). Our structural analysis combined with molecular dynamic simulations showed mHsp60(V72I) with increased inter-subunit interface, binding free energy, and dissociation force, all contributing to its enhanced subunit association stability. The gate to the nucleotide-binding (NB) site in mHsp60(V72I) mimicked the open conformation in the nucleotide-bound state with an additional open channel leading to the NB site, both promoting the mutant's ATPase activity. Our studies highlight the importance of mHsp60's characteristics in its biological function. Cryo-EM structure and molecular dynamic simulations explain the enhanced stability and ATP activity of the pathological chaperonin mutant.,Syed A, Zhai J, Guo B, Zhao Y, Wang JC, Chen L Structure. 2024 May 2;32(5):575-584.e3. doi: 10.1016/j.str.2024.02.001. Epub 2024 , Feb 26. PMID:38412855 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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