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MICROTUBULES

Cytoskeletal cryptography: structure and mechanism of an eraser

Nature Structural & Molecular Biology volume 26, pages 532–534 (2019)Cite this article

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The ‘tubulin code’, a set of post-translational modifications to the microtubule cytoskeleton that include removal of the C-terminal Tyr of α-tubulin, regulates the biological function of the polymer. Three studies now report structures of VASH1–SVBP and VASH2–SVBP heterodimers and provide insights into how these proteases recognize and cleave the terminal Tyr of α-tubulin.

The terminal, genetically encoded Tyr (or Phe, depending on the paralog) of α-tubulin is removed by vasohibin 1 (VASH1) and VASH2, a pair of enigmatic proteases that lack a canonical catalytic triad and require a second protein, called the ‘small vasohibin-binding protein’ (SVBP)1,2. VASH1–SVBP and VASH2–SVBP serve critical roles as tubulin code erasers, but how these proteases recognize and cleave the terminal Tyr of α-tubulin and what role SVBP serves in the function of VASH have remained open questions. Three articles in Nature Structural & Molecular Biology now present structural and functional analyses of the VASH1–SVBP and VASH2–SVBP heterodimers3,4,5, providing structures of the proteases in their ‘apo’ (unbound) state, bound to three different inhibitors, and in complex with an α-tubulin C-terminal peptide. These studies demonstrate the similarities between the binding of an inhibitor and that of a substrate and delineate a unique Cys-His-(carbonyl)Leu catalytic triad responsible for the catalytic mechanism and thus provide the first atomic-level view of the Tyr eraser of the tubulin code.

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Fig. 1: The proteases VASH1–SVBP and VASH2–SVBP erase the ultimate Tyr from α-tubulin.
Fig. 2: Comparative view of active sites of complexes of VASH1–SVBP and VASH2–SVBP plus inhibitor or α-tubulin.

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  1. Department of Biology, University of North Carolina, Chapel Hill, NC, USA

    Kevin C. Slep

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Correspondence to Kevin C. Slep.

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Slep, K.C. Cytoskeletal cryptography: structure and mechanism of an eraser. Nat Struct Mol Biol 26, 532–534 (2019). https://doi.org/10.1038/s41594-019-0266-2

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