دورية أكاديمية

Hub stability in the calcium calmodulin-dependent protein kinase II.

التفاصيل البيبلوغرافية
العنوان: Hub stability in the calcium calmodulin-dependent protein kinase II.
المؤلفون: Chien CT; Department of Bioengineering, and Department of Microbiology and Immunology, James H. Clark Center, Stanford University, Stanford, CA, 94305, USA.; Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, MD, 20892, USA., Puhl H; Laboratory of Biophotonics and Quantum Biology, National Institutes on Alcohol, Abuse and Alcoholism, National Institutes of Health, Rockville, MD, 208952, USA., Vogel SS; Laboratory of Biophotonics and Quantum Biology, National Institutes on Alcohol, Abuse and Alcoholism, National Institutes of Health, Rockville, MD, 208952, USA., Molloy JE; The Francis Crick Institute, London, UK.; CMCB, Warwick Medical School, Coventry, CV4 7AL, UK., Chiu W; Department of Bioengineering, and Department of Microbiology and Immunology, James H. Clark Center, Stanford University, Stanford, CA, 94305, USA. wahc@stanford.edu.; CryoEM and Bioimaging Division, Stanford Synchrotron Radiation Light source, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA, 94025, USA. wahc@stanford.edu., Khan S; Molecular Biology Consortium @ Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. smkhan@lbl.gov.
المصدر: Communications biology [Commun Biol] 2024 Jun 25; Vol. 7 (1), pp. 766. Date of Electronic Publication: 2024 Jun 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-
مواضيع طبية MeSH: Cryoelectron Microscopy* , Calcium-Calmodulin-Dependent Protein Kinase Type 2*/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2*/chemistry , Calcium-Calmodulin-Dependent Protein Kinase Type 2*/genetics , Molecular Dynamics Simulation*, Humans ; Holoenzymes/chemistry ; Holoenzymes/metabolism ; Holoenzymes/genetics ; Protein Multimerization ; Animals
مستخلص: The calcium calmodulin protein kinase II (CaMKII) is a multi-subunit ring assembly with a central hub formed by the association domains. There is evidence for hub polymorphism between and within CaMKII isoforms, but the link between polymorphism and subunit exchange has not been resolved. Here, we present near-atomic resolution cryogenic electron microscopy (cryo-EM) structures revealing that hubs from the α and β isoforms, either standalone or within an β holoenzyme, coexist as 12 and 14 subunit assemblies. Single-molecule fluorescence microscopy of Venus-tagged holoenzymes detects intermediate assemblies and progressive dimer loss due to intrinsic holoenzyme lability, and holoenzyme disassembly into dimers upon mutagenesis of a conserved inter-domain contact. Molecular dynamics (MD) simulations show the flexibility of 4-subunit precursors, extracted in-silico from the β hub polymorphs, encompassing the curvature of both polymorphs. The MD explains how an open hub structure also obtained from the β holoenzyme sample could be created by dimer loss and analysis of its cryo-EM dataset reveals how the gap could open further. An assembly model, considering dimer concentration dependence and strain differences between polymorphs, proposes a mechanism for intrinsic hub lability to fine-tune the stoichiometry of αβ heterooligomers for their dynamic localization within synapses in neurons.
(© 2024. The Author(s).)
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معلومات مُعتمدة: U24 GM129541 United States GM NIGMS NIH HHS; R01GM079429 U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS); P41GM103832 U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS); Z01 AA000452 United States ImNIH Intramural NIH HHS; United Kingdom WT_ Wellcome Trust; P41 GM103832 United States GM NIGMS NIH HHS; R01 GM079429 United States GM NIGMS NIH HHS
المشرفين على المادة: EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
0 (Holoenzymes)
تواريخ الأحداث: Date Created: 20240625 Date Completed: 20240626 Latest Revision: 20240715
رمز التحديث: 20240715
مُعرف محوري في PubMed: PMC11199487
DOI: 10.1038/s42003-024-06423-y
PMID: 38918547
قاعدة البيانات: MEDLINE