A model of the nucleotide‐binding site in tubulin

FEBS Letters

Farr, George W.¹  Yaffe, Michael B.¹  Sternlicht, Himan¹ 

[1] Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA

关键词: G-protein;    Microtubule assembly;    Protein structure;    MAPS;    microtubule-associated proteins;    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 [40];   

DOI  :  10.1016/0014-5793(87)80061-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown