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Structure paper

TitleStructure of dynein-dynactin on microtubules shows tandem adaptor binding.
Journal, issue, pagesNature, Vol. 610, Issue 7930, Page 212-216, Year 2022
Publish dateSep 7, 2022
AuthorsSami Chaaban / Andrew P Carter /
PubMed AbstractCytoplasmic dynein is a microtubule motor that is activated by its cofactor dynactin and a coiled-coil cargo adaptor. Up to two dynein dimers can be recruited per dynactin, and interactions between ...Cytoplasmic dynein is a microtubule motor that is activated by its cofactor dynactin and a coiled-coil cargo adaptor. Up to two dynein dimers can be recruited per dynactin, and interactions between them affect their combined motile behaviour. Different coiled-coil adaptors are linked to different cargos, and some share motifs known to contact sites on dynein and dynactin. There is limited structural information on how the resulting complex interacts with microtubules and how adaptors are recruited. Here we develop a cryo-electron microscopy processing pipeline to solve the high-resolution structure of dynein-dynactin and the adaptor BICDR1 bound to microtubules. This reveals the asymmetric interactions between neighbouring dynein motor domains and how they relate to motile behaviour. We found that two adaptors occupy the complex. Both adaptors make similar interactions with the dyneins but diverge in their contacts with each other and dynactin. Our structure has implications for the stability and stoichiometry of motor recruitment by cargos.
External linksNature / PubMed:36071160 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 20.0 Å
Structure data

14549

7z8f

EMDB-14549, PDB-7z8f:
Composite structure of dynein-dynactin-BICDR on microtubules
Method: EM (single particle) / Resolution: 20.0 Å

14550

7z8g

EMDB-14550, PDB-7z8g:
Cytoplasmic dynein-1 motor domain
Method: EM (single particle) / Resolution: 3.52 Å

14551

7z8h

EMDB-14551, PDB-7z8h:
Cytoplasmic dynein-1 motor domain AAA1, AAA2, and AAA3 subunits
Method: EM (single particle) / Resolution: 3.41 Å

14552

7z8i

EMDB-14552, PDB-7z8i:
The barbed end complex of dynactin bound to BICDR1 and the cytoplasmic dynein tails (A2, B1, B2)
Method: EM (single particle) / Resolution: 3.3 Å

14553

7z8j

EMDB-14553, PDB-7z8j:
Cytoplasmic dynein (A2) bound to BICDR1
Method: EM (single particle) / Resolution: 3.93 Å

14555

7z8k

EMDB-14555, PDB-7z8k:
Cytoplasmic dynein (A1) bound to BICDR1
Method: EM (single particle) / Resolution: 4.37 Å

14556

7z8l

EMDB-14556, PDB-7z8l:
Cytoplasmic dynein light intermediate chain (B1) bound to the motor domain (A2).
Method: EM (single particle) / Resolution: 4.9 Å

14559

7z8m

EMDB-14559, PDB-7z8m:
The pointed end complex of dynactin bound to BICDR1
Method: EM (single particle) / Resolution: 3.37 Å

EMDB-15396: Consensus map of dynein-dynactin-BICDR on microtubules
Method: EM (single particle) / Resolution: 6.33 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-ZN:
Unknown entry

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
  • sus scrofa (pig)
  • mus musculus (house mouse)
KeywordsSTRUCTURAL PROTEIN / Dynein / dynactin / cargo transport / activating adaptor / cytoskeleton

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