+
Open data
-
Basic information
Entry | Database: PDB / ID: 6w4o | ||||||
---|---|---|---|---|---|---|---|
Title | CaMKII alpha-30 Cryo-EM reconstruction | ||||||
![]() | (Calcium/calmodulin-dependent protein kinase type II subunit alpha![]() | ||||||
![]() | ![]() ![]() ![]() ![]() | ||||||
Function / homology | ![]() peptidyl-threonine autophosphorylation / regulation of endocannabinoid signaling pathway / calcium- and calmodulin-dependent protein kinase complex / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Chao, L.H. / Stratton, M.M. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Heterogeneity in human hippocampal CaMKII transcripts reveals allosteric hub-dependent regulation. Authors: Roman Sloutsky / Noelle Dziedzic / Matthew J Dunn / Rachel M Bates / Ana P Torres-Ocampo / Sivakumar Boopathy / Brendan Page / John G Weeks / Luke H Chao / Margaret M Stratton / ![]() Abstract: Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes ...Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIβ, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulatory segment, a variable linker region, and a hub domain, which is responsible for oligomerization. The four proteins differ primarily in linker length and composition because of extensive alternative splicing. Here, we report the heterogeneity of CaMKII transcripts in three complex samples of human hippocampus using deep sequencing. We showed that hippocampal cells contain a diverse collection of over 70 CaMKII transcripts from all four CaMKII-encoding genes. We characterized the Ca/CaM sensitivity of hippocampal CaMKII variants spanning a broad range of linker lengths and compositions. The effect of the variable linker on Ca/CaM sensitivity depended on the kinase and hub domains. Moreover, we revealed a previously uncharacterized role for the hub domain as an allosteric regulator of kinase activity, which may provide a pharmacological target for modulating CaMKII activity. Using small-angle x-ray scattering and single-particle cryo-electron microscopy (cryo-EM), we present evidence for extensive interactions between the kinase and the hub domains, even in the presence of a 30-residue linker. Together, these data suggest that Ca/CaM sensitivity in CaMKII is homolog dependent and includes substantial contributions from the hub domain. Our sequencing approach, combined with biochemistry, provides insights into understanding the complex pool of endogenous CaMKII splice variants. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 801.2 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 638.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 21535MC ![]() 6w4pC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | ![]() Mass: 53633.953 Da / Num. of mol.: 12 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() References: UniProt: Q9UQM7, ![]() #2: Protein | | ![]() Mass: 53634.984 Da / Num. of mol.: 1 / Mutation: K37M Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() References: UniProt: Q9UQM7, ![]() |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
-
Sample preparation
Component | Name: CaMKII alpha-30 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Specimen support | Details: 30 mA for 30 s using PELCO easiGlow / Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: C-flat-1.2/1.3 |
Vitrification![]() | Instrument: GATAN CRYOPLUNGE 3 / Cryogen name: ETHANE / Humidity: 96 % |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: OTHER |
Image recording | Electron dose: 52 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-
Processing
EM software |
| |||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 4.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 160211 / Symmetry type: POINT | |||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | |||||||||||||||||||||||||||
Atomic model building |
|