Journal: EMBO J / Year: 2021 Title: Cryo-EM reveals the complex architecture of dynactin's shoulder region and pointed end. Authors: Clinton K Lau / Francis J O'Reilly / Balaji Santhanam / Samuel E Lacey / Juri Rappsilber / Andrew P Carter / Abstract: Dynactin is a 1.1 MDa complex that activates the molecular motor dynein for ultra-processive transport along microtubules. In order to do this, it forms a tripartite complex with dynein and a coiled- ...Dynactin is a 1.1 MDa complex that activates the molecular motor dynein for ultra-processive transport along microtubules. In order to do this, it forms a tripartite complex with dynein and a coiled-coil adaptor. Dynactin consists of an actin-related filament whose length is defined by its flexible shoulder domain. Despite previous cryo-EM structures, the molecular architecture of the shoulder and pointed end of the filament is still poorly understood due to the lack of high-resolution information in these regions. Here we combine multiple cryo-EM datasets and define precise masking strategies for particle signal subtraction and 3D classification. This overcomes domain flexibility and results in high-resolution maps into which we can build the shoulder and pointed end. The unique architecture of the shoulder securely houses the p150 subunit and positions the four identical p50 subunits in different conformations to bind dynactin's filament. The pointed end map allows us to build the first structure of p62 and reveals the molecular basis for cargo adaptor binding to different sites at the pointed end.
History
Deposition
Jul 6, 2020
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Header (metadata) release
Jul 29, 2020
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Map release
Jul 29, 2020
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Update
May 1, 2024
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Current status
May 1, 2024
Processing site: PDBe / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Protein or peptide: ARP1 actin related protein 1 homolog A
Protein or peptide: Actin, cytoplasmic 1
Protein or peptide: Arp11
Protein or peptide: Dynactin subunit 2
Protein or peptide: Dynactin 6
Protein or peptide: Dynactin subunit 5
Protein or peptide: Dynactin subunit 4
Complex: BICDR1
Protein or peptide: BICD family-like cargo adapter 1,BICD family-like cargo adapter 1,BICDR1
Ligand: ADENOSINE-5'-DIPHOSPHATE
Ligand: ADENOSINE-5'-TRIPHOSPHATE
Ligand: ZINC ION
+
Supramolecule #1: Dynein-Dynactin-BICDR1 complex
Supramolecule
Name: Dynein-Dynactin-BICDR1 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#8 Details: Note that signal for dyneins and part of dynactin and BICDR1 have been removed by signal subtraction
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