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A model of the nucleotide‐binding site in tubulin
Author(s) -
Sternlicht Himan,
Yaffe Michael B.,
Farr George W.
Publication year - 1987
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(87)80061-3
Subject(s) - gtp' , tubulin , nucleotide , microtubule , binding site , biology , peptide sequence , amino acid , protein structure , biochemistry , microbiology and biotechnology , gene , enzyme
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.