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 unstruc-tured 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 com-bination of H 1 andH 2 inhibits tubulin polymerization, while the combination of H 1 and the N-terminus is less efficient. None of the individual three regions alone are functional in this respect. However, all of them cross-link to α-tubulin, but only full-length stathmin produces high-molecular-weight products. Mass spec-trometry analysis of α-tubulin–stathmin/OP18 and its truncation products shows that full-length stathmin/ OP18 binds to the region around helix 10 of α-tubulin, a region that is involved in longitudinal interactions in theMT, sequestering the dimer and possibly linking two tubulin heterodimers. In the absence of the N-terminus, stathmin/OP18 binds to only one molecule of α-tubulin, at the top of the free tubulin heterodimer, preventing polymerization