Molecular basis for substrate recognition by MTMR2, a myotubularin family phosphoinositide phosphatase.

ABSTRACT: Myotubularins, a large family of catalytically active and inactive proteins, belong to a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as physiological substrates. Here, by integrating crystallographic and deuterium-exchange mass spectrometry studies of human myotubularin-related protein-2 (MTMR2) in complex with phosphoinositides, we define the molecular basis for this unique substrate specificity. Phosphoinositide substrates bind in a pocket located on a positively charged face of the protein, suggesting an electrostatic mechanism for membrane targeting. A flexible, hydrophobic helix makes extensive interactions with the diacylglycerol moieties of substrates, explaining the specificity for membrane-bound phosphoinositides.

SUBMITTER: Begley MJ 

PROVIDER: S-EPMC1347996 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature