6hc2

Crystal structure of NuMA/LGN hetero-hexamers

spinqualitylabelsall models 6hc2, resolution 4.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6hc2 is a 24 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [GPSM2_HUMAN] Autosomal recessive nonsyndromic sensorineural deafness type DFNB;Chudley-McCullough syndrome. Chudley-McCullough syndrome (CMCS) [MIM:604213]: An autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal. Note=The disease is caused by mutations affecting the gene represented in this entry. [NUMA1_HUMAN] Acute promyelocytic leukemia. Function [GPSM2_HUMAN] Plays an important role in spindle pole orientation. Interacts and contributes to the functional activity of G(i) alpha proteins. Acts to stabilize the apical complex during neuroblast divisions. [NUMA1_HUMAN] Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority if the nuclear volume. Required for maintenance and establishment of the mitotic spindle poles, functionning as a tether linking bulk microtubules of the spindle to centrosomes. May be involved in coordination of the alignment of the mitotic spindle to the cellular polarity axis, which is a prerequisite for asymmetric cell divisions. Publication Abstract from PubMed Cortical force generators connect epithelial polarity sites with astral microtubules, allowing dynein movement to orient the mitotic spindle as astral microtubules depolymerize. Complexes of the LGN and NuMA proteins, fundamental components of force generators, are recruited to the cortex by Galphai-subunits of heterotrimeric G-proteins. They associate with dynein/dynactin and activate the motor activity pulling on astral microtubules. The architecture of cortical force generators is unknown. Here we report the crystal structure of NuMA:LGN hetero-hexamers, and unveil their role in promoting the assembly of active cortical dynein/dynactin motors that are required in orchestrating oriented divisions in polarized cells. Our work elucidates the basis for the structural organization of essential spindle orientation motors. Hexameric NuMA:LGN structures promote multivalent interactions required for planar epithelial divisions.,Pirovano L, Culurgioni S, Carminati M, Alfieri A, Monzani S, Cecatiello V, Gaddoni C, Rizzelli F, Foadi J, Pasqualato S, Mapelli M Nat Commun. 2019 May 17;10(1):2208. doi: 10.1038/s41467-019-09999-w. PMID:31101817 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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