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A novel bipartite phospholipid‐binding module in the neurofibromatosis type 1 protein
Author(s) -
D'angelo Igor,
Welti Stefan,
Bonneau Fabien,
Scheffzek Klaus
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400602
Subject(s) - bipartite graph , neurofibromatosis , type (biology) , phospholipid , genetics , computational biology , biology , microbiology and biotechnology , computer science , theoretical computer science , graph , ecology , membrane
Neurofibromatosis type 1 (NF1) is a common tumour predisposition syndrome associated with numerous clinical complications. Mutations in the tumour suppressor gene NF1 are responsible for disease pathogenesis. This gene encodes the 320 kDa protein neurofibromin, the only clearly defined function of which is to act as a Ras‐specific GTPase‐activating protein (RasGAP). Here we report the structural discovery of a novel module in neurofibromin, composed of a Sec14p homologous segment and a previously undetected pleckstrin homology (PH)‐like domain of potentially novel function. We show phospholipid binding by this bipartite module and identify residues that are involved in this activity; we also show that the PH‐like domain is not sufficient for lipid binding. The unique architecture of the domain interface points to a model of how the PH‐like domain may regulate binding of a ligand by the Sec14 module.