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The structure and regulation of myotubularin phosphatases

Michael J Begley1, Jack E Dixon

  • 1Department of Pharmacology, University of California, San Diego, La Jolla, CA 2093-0721, USA.

Current Opinion in Structural Biology
|November 18, 2005
PubMed

Insights

Mutations in myotubularin proteins cause neuromuscular diseases. Structural and biochemical studies reveal how these protein tyrosine phosphatases bind inositol phospholipids and how inactive members regulate active ones.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Background:

  • Myotubularin family proteins are linked to neuromuscular disorders like X-linked myotubular myopathy and Charcot-Marie-Tooth disease type 4B.
  • These proteins belong to a unique subfamily of protein tyrosine phosphatases with distinct substrate specificity.

Purpose of the Study:

  • To define the structural features of myotubularin family proteins.
  • To elucidate the molecular basis of their unique substrate specificity.
  • To understand the regulatory roles of catalytically inactive myotubularins.

Main Methods:

  • X-ray crystallography to determine the first crystal structure of a myotubularin family protein.
  • Biochemical assays to study substrate specificity and protein interactions.

Main Results:

  • Structural studies revealed characteristic features of the myotubularin family and the basis for their inositol phospholipid substrate specificity.
  • Biochemical studies identified a subgroup of catalytically inactive myotubularins.

Conclusions:

  • Inactive myotubularins function as adaptors for active members, playing a crucial regulatory role.
  • Understanding myotubularin structure and function provides insights into neuromuscular disease mechanisms.

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