Asymmetric Coiled-Coil Structure with Guanine Nucleotide Exchange Activity

Yusuke Sato, Ryutaro Shirakawa, Hisanori Horiuchi, Naoshi Dohmae, Shuya Fukai, Osamu Nureki

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Vesicular traffic during exocytosis is regulated by Rab GTPase, Sec4p in yeast, which is activated by a guanine nucleotide exchange factor (GEF) called Sec2p. The GEF activity is localized in the N-terminal 160 residues of Sec2p, which lacks sequence similarity with any other GEFs with known structures, and thereby the guanine nucleotide exchange mechanism by Sec2p remains unknown. Here, we report the crystal structure of the Sec2p GEF domain at 3.0 Å resolution. The structure unexpectedly consists of a homodimeric, parallel coiled coil that extends over 180 Å. Pull-down and guanine nucleotide exchange analyses on a series of deletion and point mutants of Sec2p unveiled the catalytic residues for its GEF activity as well as the Sec4p binding site, thus presenting a nucleotide exchange mechanism by a simple coiled coil. The present functional analyses allow us to build the Sec2p:Sec4p complex model, which explains the specificity for Rab GTPases by their respective GEF proteins.

Original languageEnglish
Pages (from-to)245-252
Number of pages8
Issue number2
Publication statusPublished - 2007 Feb


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