6ys4
From Proteopedia
Structure of the Homo sapiens SAS-6 coiled-coil domain
Structural highlights
Disease[SAS6_HUMAN] Autosomal recessive primary microcephaly. The disease is caused by variants affecting the gene represented in this entry. Function[SAS6_HUMAN] Central scaffolding component of the centrioles ensuring their 9-fold symmetry. Required for centrosome biogenesis and duplication: required both for mother-centriole-dependent centriole duplication and deuterosome-dependent centriole amplification in multiciliated cells. Overexpression results in excess foci-bearing centriolar markers. Required for the recruitment of STIL to the procentriole and for STIL-mediated centriole amplification (PubMed:22020124).[1] [2] [3] [4] Publication Abstract from PubMedCentrioles are eukaryotic organelles that template the formation of cilia and flagella, as well as organize the microtubule network and the mitotic spindle in animal cells. Centrioles have proximal-distal polarity and a 9-fold radial symmetry imparted by a likewise symmetrical central scaffold, the cartwheel. The spindle assembly abnormal protein 6 (SAS-6) self-assembles into 9-fold radially symmetric ring-shaped oligomers that stack via an unknown mechanism to form the cartwheel. Here, we uncover a homo-oligomerization interaction mediated by the coiled-coil domain of SAS-6. Crystallographic structures of Chlamydomonas reinhardtii SAS-6 coiled-coil complexes suggest this interaction is asymmetric, thereby imparting polarity to the cartwheel. Using a cryoelectron microscopy (cryo-EM) reconstitution assay, we demonstrate that amino acid substitutions disrupting this asymmetric association also impair SAS-6 ring stacking. Our work raises the possibility that the asymmetric interaction inherent to SAS-6 coiled-coil provides a polar element for cartwheel assembly, which may assist the establishment of the centriolar proximal-distal axis. Structures of SAS-6 coiled coil hold implications for the polarity of the centriolar cartwheel.,Kantsadi AL, Hatzopoulos GN, Gonczy P, Vakonakis I Structure. 2022 Feb 22. pii: S0969-2126(22)00041-7. doi:, 10.1016/j.str.2022.02.005. PMID:35240058[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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