Structural Biology

Spastin uses its network

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Science  23 Aug 2019:
Vol. 365, Issue 6455, pp. 770-771
DOI: 10.1126/science.365.6455.770-f

AAA ATPases are adenosine triphos phatases associated with diverse cellular activities that have a conserved module of amino acid residues. Spastin is an AAA ATPase protein that severs microtubules. Mutations in spastin cause hereditary spastic paraplegias. Microtubule severing seems to occur when spastin protomers form a hexamer around a polyglutamated tubulin tail and pull the tubulin subunit out of the microtubule lattice. Sandate et al. report a cryo–electron microscopy structure of the spastin hexamer bound to ATP and a polyglutamate peptide. Comparison to an apo-monomer structure shows that ATP binding drives the conformational changes required for oligomerization. Each protomer has three conserved loops. Two loops form a double helical staircase that surrounds the substrate, and the third links the substrate-interacting loops to the nucleotide binding pocket. Thus, ATP and peptide binding establish a network of interactions that stabilize the hexamer and facilitate efficient severing.

Nat. Struct. Mol. Biol. 26, 671 (2019).

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