Journal article
Lst4, the yeast Fnip1/2 orthologue, is a DENN-family protein
A Pacitto, DB Ascher, LH Wong, BK Blaszczyk, RK Nookala, N Zhang, S Dokudovskaya, TP Levine, TL Blundell
Open Biology | ROYAL SOC | Published : 2015
DOI: 10.1098/rsob.150174
Abstract
The folliculin/Fnip complex has been demonstrated to play a crucial role in the mechanisms underlying Birt-Hogg-Dubé (BHD) syndrome, a rare inherited cancer syndrome. Lst4 has been previously proposed to be the Fnip 1/2 orthologue in yeast and therefore a member of the DENN family. In order to confirm this, we solved the crystal structure of the N-terminal region of Lst4 from Kluyveromyces lactis and show it contains a longin domain, the first domain of the full DENN module. Furthermore, we demonstrate that Lst4 through its DENN domain interacts with Lst7, the yeast folliculin orthologue. Like its human counterpart, the Lst7/Lst4 complex relocates to the vacuolar membrane in response to nutr..
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Awarded by Ligue Contre le Cancer
Funding Acknowledgements
A.P., B.K.B. and R.K.N. were supported by the Myrovlytis Trust. D.B.A. was supported by a NHMRC CJ Martin Fellowship (APP1072476). L.H.W. was supported by a Medical Research Council (MRC) studentship, MR/J006580/1, and T.P.L. by University College London. S.D. was supported by Fondation de France, La Ligue National contre le Cancer (Comite de Paris/Ile-de-France and Comite de l'Oise); T.L.B and N.Z. thank the University of Cambridge and The Wellcome Trust for facilities and support.