Abstract
Tubulin uses GTP to regulate microtubule assembly and is thought to be a member of a class of GDP/GTP‐binding proteins (G‐proteins) as defined by Hughes [(1983) Febs Lett. 164, 1–8]. How tubulin is structurally related to G‐proteins is not known. We use a synthesis of sequence comparisons between tubulin, other G‐proteins, and ADP/ATP‐binding proteins and topological arguments to identify potential regions involved in nucleotide binding. We propose that the nucleotide‐binding domain in the β‐subunit of tubulin is an α/β structure derived from amino acid residues ∼60–300. Five peptide sequences are identified which we suggest exist as ‘loops’ that extend from β‐strands and connect α‐helices in this structure. We argue that GDP binds to four of the five loops in an Mg2+‐independent manner while GTP binds in an Mg2+‐dependent manner to a different combination of four loops. We propose that this switch between loops upon GTP binding induces a conformational change essential for microtubule assembly.
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Dates
Type | When |
---|---|
Created | 23 years ago (July 25, 2002, 5:12 a.m.) |
Deposited | 1 year, 11 months ago (Sept. 16, 2023, 3:10 a.m.) |
Indexed | 1 year, 7 months ago (Jan. 15, 2024, 1 a.m.) |
Issued | 38 years, 4 months ago (April 20, 1987) |
Published | 38 years, 4 months ago (April 20, 1987) |
Published Online | 23 years, 10 months ago (Oct. 19, 2001) |
Published Print | 38 years, 4 months ago (April 20, 1987) |
@article{Sternlicht_1987, title={A model of the nucleotide‐binding site in tubulin}, volume={214}, ISSN={1873-3468}, url={http://dx.doi.org/10.1016/0014-5793(87)80061-3}, DOI={10.1016/0014-5793(87)80061-3}, number={2}, journal={FEBS Letters}, publisher={Wiley}, author={Sternlicht, Himan and Yaffe, Michael B. and Farr, George W.}, year={1987}, month=apr, pages={226–235} }