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Structure paper

TitleMolecular mechanism of dynein-dynactin complex assembly by LIS1.
Journal, issue, pagesScience, Vol. 383, Issue 6690, Page eadk8544, Year 2024
Publish dateMar 29, 2024
AuthorsKashish Singh / Clinton K Lau / Giulia Manigrasso / José B Gama / Reto Gassmann / Andrew P Carter /
PubMed AbstractCytoplasmic dynein is a microtubule motor vital for cellular organization and division. It functions as a ~4-megadalton complex containing its cofactor dynactin and a cargo-specific coiled-coil ...Cytoplasmic dynein is a microtubule motor vital for cellular organization and division. It functions as a ~4-megadalton complex containing its cofactor dynactin and a cargo-specific coiled-coil adaptor. However, how dynein and dynactin recognize diverse adaptors, how they interact with each other during complex formation, and the role of critical regulators such as lissencephaly-1 (LIS1) protein (LIS1) remain unclear. In this study, we determined the cryo-electron microscopy structure of dynein-dynactin on microtubules with LIS1 and the lysosomal adaptor JIP3. This structure reveals the molecular basis of interactions occurring during dynein activation. We show how JIP3 activates dynein despite its atypical architecture. Unexpectedly, LIS1 binds dynactin's p150 subunit, tethering it along the length of dynein. Our data suggest that LIS1 and p150 constrain dynein-dynactin to ensure efficient complex formation.
External linksScience / PubMed:38547289 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 10.0 Å
Structure data

EMDB-17825, PDB-8pqv:
Cytoplasmic dynein-1 motor domain in post-powerstroke state
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-17826, PDB-8pqw:
Cytoplasmic dynein-1 motor domain bound to dynactin-p150glued and LIS1
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-17828, PDB-8pqy:
Cytoplasmic dynein-1 motor domain bound to LIS1
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-17829, PDB-8pqz:
Cytoplasmic dynein-1 A1/A2 motor domains bound to LIS1
Method: EM (single particle) / Resolution: 5.5 Å

EMDB-17830, PDB-8pr0:
Cytoplasmic dynein-A heavy chain bound to dynactin-p150glued and IC-LC tower
Method: EM (single particle) / Resolution: 9.4 Å

EMDB-17831, PDB-8pr1:
Cytoplasmic dynein-B heavy chain bound to IC-LC tower
Method: EM (single particle) / Resolution: 8.2 Å

EMDB-17832, PDB-8pr2:
Cytoplasmic dynein-1 heavy chain bound to JIP3-LZI
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-17833, PDB-8pr3:
Cytoplasmic dynein-1 heavy chain bound to JIP3-RH1
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-17834, PDB-8pr4:
Dynactin pointed end bound to JIP3
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-17835: Consensus cryo-EM structure of Dynein-Dynactin-JIP3(1-185)-LIS1
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-17836: Consensus cryo-EM structure of Dynein-dynactin-JIP3(1-560)-LIS1
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-17873, PDB-8ptk:
Composite structure of Dynein-Dynactin-JIP3-LIS1
Method: EM (single particle) / Resolution: 10.0 Å

PDB-8pr5:
Structure of the autoinhibited dynactin p150glued projection
Method: ELECTRON MICROSCOPY / Resolution: 8.6 Å

Chemicals

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

ChemComp-MG:
Unknown entry

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

ChemComp-ZN:
Unknown entry

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

Source
  • homo sapiens (human)
  • sus scrofa (pig)
KeywordsMOTOR PROTEIN / Dynein / AAA-Atpase / p150 / LIS1 / dynactin / LC8 / TCTEX1 / JIP3

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