CMT 4B and The structure and regulation of myotubularin phosphatases.

[Guest guest]

Curr Opin Struct Biol. 2005 Nov 7;

The structure and regulation of myotubularin phosphatases.

Begley MJ, Dixon JE.

Departments of Pharmacology, Cellular and Molecular Medicine, and

Chemistry and Biochemistry, University of California, San Diego, La

Jolla, CA 2093-0721, USA.

The human neuromuscular diseases X-linked myotubular myopathy and

Charcot-Marie-Tooth disease type 4B are caused by mutations in

myotubularin family proteins. The myotubularins are a unique

subfamily of protein tyrosine phosphatases that utilize inositol

phospholipids, rather than phosphoproteins, as substrates. Recent

structural studies, including the first crystal structure of a

myotubularin family protein, have defined the structural features

that are characteristic of the family and revealed the molecular

basis of their unique substrate specificity. Interestingly, the

myotubularin family contains a subgroup of proteins that are

catalytically inactive. Recent biochemical studies have established

that the inactive myotubularins function as adaptors for the active

members and play an important regulatory role within the family.