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 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 alpha-tubulin, but only full-length stathmin produces high-molecular-weight products. Mass spectrometry analysis of alpha-tubulin-stathmin/OP18 and its truncation 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 tubulin heterodimers. In the absence of the N-terminus, stathmin/OP18 binds to only one molecule of alpha-tubulin, at the top of the free tubulin heterodimer, preventing polymerization.
Wallon
G
G
Structural Biology Program, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany. wallon@embl-heidelberg.de
Rappsilber
J
J
Mann
M
M
Serrano
L
L
D003001:Cloning, Molecular; D006801:Humans; D008868:Microtubule Proteins; D008870:Microtubules / Q000648:ultrastructure; D008958:Models, Molecular; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D050777:Stathmin; D013816:Thermodynamics; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism*
D008868:Microtubule Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C493995:STMN1 protein, human; D050777:Stathmin; D014404:Tubulin