6mrc | pdb_00006mrc
ADP-bound human mitochondrial Hsp60-Hsp10 football complex
Structural highlights
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. [CH10_HUMAN] Eukaryotic CPN10 homolog which is essential for mitochondrial protein biogenesis, together with CPN60. Binds to CPN60 in the presence of Mg-ATP and suppresses the ATPase activity of the latter. Publication Abstract from PubMedmHsp60-mHsp10 assists the folding of mitochondrial matrix proteins without the negative ATP binding inter-ring cooperativity of GroEL-GroES. Here we report the crystal structure of an ATP (ADP:BeF3-bound) ground-state mimic double-ring mHsp6014-(mHsp107)2 football complex, and the cryo-EM structures of the ADP-bound successor mHsp6014-(mHsp107)2 complex, and a single-ring mHsp607-mHsp107 half-football. The structures explain the nucleotide dependence of mHsp60 ring formation, and reveal an inter-ring nucleotide symmetry consistent with the absence of negative cooperativity. In the ground-state a two-fold symmetric H-bond and a salt bridge stitch the double-rings together, whereas only the H-bond remains as the equatorial gap increases in an ADP football poised to split into half-footballs. Refolding assays demonstrate obligate single- and double-ring mHsp60 variants are active, and complementation analysis in bacteria shows the single-ring variant is as efficient as wild-type mHsp60. Our work provides a structural basis for active single- and double-ring complexes coexisting in the mHsp60-mHsp10 chaperonin reaction cycle. Structural basis for active single and double ring complexes in human mitochondrial Hsp60-Hsp10 chaperonin.,Gomez-Llorente Y, Jebara F, Patra M, Malik R, Nisemblat S, Chomsky-Hecht O, Parnas A, Azem A, Hirsch JA, Ubarretxena-Belandia I Nat Commun. 2020 Apr 21;11(1):1916. doi: 10.1038/s41467-020-15698-8. PMID:32317635[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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