6f38
Cryo-EM structure of two dynein tail domains bound to dynactin and HOOK3
Structural highlights
Disease[DYHC1_HUMAN] Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures;Autosomal dominant non-syndromic intellectual disability;Autosomal dominant Charcot-Marie-Tooth disease type 2O. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function[DC1L2_HUMAN] Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes. [ACTB_PIG] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [DLRB1_HUMAN] Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. [DC1I2_HUMAN] Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150-glued) DCNT1. Involved in membrane-transport, such as Golgi apparatus, late endosomes and lysosomes. [DYHC1_HUMAN] Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Plays a role in mitotic spindle assembly and metaphase plate congression (PubMed:27462074).[1] Publication Abstract from PubMedDynein and its cofactor dynactin form a highly processive microtubule motor in the presence of an activating adaptor, such as BICD2. Different adaptors link dynein and dynactin to distinct cargoes. Here we use electron microscopy and single-molecule studies to show that adaptors can recruit a second dynein to dynactin. Whereas BICD2 is biased towards recruiting a single dynein, the adaptors BICDR1 and HOOK3 predominantly recruit two dyneins. We find that the shift towards a double dynein complex increases both the force and speed of the microtubule motor. Our 3.5 A resolution cryo-electron microscopy reconstruction of a dynein tail-dynactin-BICDR1 complex reveals how dynactin can act as a scaffold to coordinate two dyneins side-by-side. Our work provides a structural basis for understanding how diverse adaptors recruit different numbers of dyneins and regulate the motile properties of the dynein-dynactin transport machine. Cryo-EM shows how dynactin recruits two dyneins for faster movement.,Urnavicius L, Lau CK, Elshenawy MM, Morales-Rios E, Motz C, Yildiz A, Carter AP Nature. 2018 Feb 7;554(7691):202-206. doi: 10.1038/nature25462. PMID:29420470[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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