A model of the nucleotide-binding site in tubulin

• Published in: FEBS letters Vol. 214; no. 2; pp. 226 - 235
• Main Authors: Sternlicht, Himan, Yaffe, Michael B., Farr, George W.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20-04-1987; Elsevier
• Subjects: Amino Acid Sequence; Binding Sites; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; G protein; GTP-Binding Proteins - metabolism; Guanosine Diphosphate - metabolism; Guanosine Triphosphate - metabolism; Interactions. Associations; Intermolecular phenomena; MAPS, microtubule-associated proteins; Microtubule assembly; microtubules; Models, Molecular; Molecular biophysics; nucleotides; Protein Conformation; Protein structure; tubulin; Tubulin - metabolism; α/β, a type of fold observed in proteins consisting of β-strands and their interconnecting α-helices organized as a sheet of predominantly parallel β-strands with the α-helices packed against the front and back faces of the sheet; α/β, a type of fold observed in proteins consisting of β-strands and their interconnecting α-helices organized as a sheet of predominantly parallel β-strands with the α-helices packed against the front and back faces of the sheet; G-protein; Microtubule assembly; Protein structure; MAPS, microtubule-associated proteins; GTP; Tubulin; Guanosine diphosphate; Guanine nucleotide; Molecular association; Nucleotide; Contractile protein; Models; Binding site; Conformation
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(87)80061-3

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 Mg
2+-
independent manner while GTP binds in an Mg
2+-
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.