5v47

Crystal structure of the SR1 domain of lizard sacsin

spinqualitylabelsall models 5v47, resolution 1.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5v47 is a 2 chain structure with sequence from Anolis carolinensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.84Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G1KBF9_ANOCA Publication Abstract from PubMed Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disease that is caused by mutations in the SACS gene. The product of this gene is a very large 520 kDa cytoplasmic protein, sacsin, with an ubiquitin-like domain (Ubl) at the N-terminus followed by three large sacsin internal repeats (SIRPTs) supradomains and C-terminal J and HEPN domains. The SIRPTs are predicted to contain Hsp90-like domains suggesting a potential chaperone activity. In this work, we report the structures of the Hsp90-like Sr1 domain of SIRPT1 and the N-terminal Ubl domain determined at 1.55 A and 2.1 A resolution, respectively. The Ubl domain crystallized as a swapped dimer that could be relevant in the context of full-length protein. The Sr1 domain displays the Bergerat protein fold with a characteristic nucleotide-binding pocket, though it binds nucleotides with very low affinity. The Sr1 structure reveals that ARSACS-causing missense mutations (R272H, R272C and T201K) disrupt protein folding most likely leading to sacsin degradation. This work lends a structural support to the view of sacsin as a molecular chaperone and provides a framework for future studies of this protein. Structures of Ubl and Hsp90-like domains of sacsin provide insight into pathological mutations.,Menade M, Kozlov G, Trempe JF, Pande H, Shenker S, Wickremasinghe S, Li X, Hojjat H, Dicaire MJ, Brais B, McPherson PS, Wong MJH, Young JC, Gehring K J Biol Chem. 2018 Jun 26. pii: RA118.003939. doi: 10.1074/jbc.RA118.003939. PMID:29945973 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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