Model for stathmin/OP18 binding to tubulin

Stathmin/OP18 is a regulatory phosphoprotein that controls microtubule (MT) dynamics, The protein does not have a defined three-dimensional structure, although it contains three distinct regions (an unstructured N-terminus, N : 1-44; a region with high helix propensity, H 1: 44-89; and a region with low helix propensity, H 2: 90-142). The full protein and a combination of H 1 and H 2 inhibits tubulin polymerization, while the combination of H 1 an d the N-terminus is less efficient. None of the individual three regions al one are functional in this respect. However, all of them cross-link to alph a-tubulin, but only full-length stathmin produces high-molecular-weight pro ducts. Mass spectrometry analysis of alpha-tubulin-stathmin/OP18 and its tr uncation products shows that full-length stathmin/OP18 binds to the region around helix 10 of alpha-tubulin, a region that is involved in longitudinal interactions in the MT, sequestering the dimer and possibly linking two tu bulin heterodimers, In the absence of the N-terminus, stathmin/OP18 binds t o only one molecule of alpha-tubulin, at the top of the free tubulin hetero dimer, preventing polymerization.