Structures of TOG1 and TOG2 from the human microtubule dynamics regulator CLASP1
Fig 8
Model of CLASP family TOG domain structures and potential tubulin binding modes.
TOG domains and tubulin are colored as presented in Fig 6A. From top to bottom: H.s. CLASP1 TOG1 (orange) is architecturally similar to the TOG domains of the XMAP215 family member S.c. Stu2. While no tubulin- or microtubule-binding activity has been detected for CLASP family TOG1 domains, a role in cellular localization and autoregulation has been reported. H.s. CLASP1 TOG2 (blue) has a convex TOG architecture across its tubulin-binding surface that may be used to engage tubulin in a hypercurved state and may underlie the anti-catastrophe and rescue activity reported for the structurally similar H.s. CLASP2 TOG2 domain. M.m. CLASP2 TOG3 (purple) also has a convex architecture across its tubulin-binding surface, but is not bent as dramatically as H.s. CLASP1 TOG2. The convex M.m. CLASP2 TOG3 architecture may be used to engage a curved tubulin state. Relative to the other CLASP family TOG domains presented, the M.m. CLASP2 TOG3 domain has a unique architectural shift in the plane tangential to the microtubule surface and orthogonal to its tubulin-binding surface. This shift may enable it to engage the laterally associated tubulin subunit on the neighboring protofilament and support the reported ability of H.s. CLASP2 TOG3 to promote microtubule rescue.