Related Experiment Video

Updated: Jun 24, 2026

Rapid Genotyping of Animals Followed by Establishing Primary Cultures of Brain Neurons
09:51

Rapid Genotyping of Animals Followed by Establishing Primary Cultures of Brain Neurons

Published on: January 29, 2015

Structure of dystrophia myotonica protein kinase

Jonathan M Elkins1, Ann Amos, Frank H Niesen

  • 1Structural Genomics Consortium, Nuffield Department of Medicine, Oxford University, Old Road Campus Research Building, Oxford, OX3 7DQ, United Kingdom.

Protein Science : a Publication of the Protein Society
|March 25, 2009
PubMed

Insights

Dystrophia myotonica protein kinase (DMPK) forms dimers through its coiled-coil domains, not just the kinase domain. The crystal structure reveals BIM-8 inhibitor binding in an active kinase conformation.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Background:

  • Dystrophia myotonica protein kinase (DMPK) is a serine/threonine kinase with kinase and coiled-coil domains.
  • DMPK is implicated in cellular processes through its multimerization capabilities.

Purpose of the Study:

  • To elucidate the structural basis of DMPK dimerization and its active conformation.
  • To understand the binding interaction of the inhibitor bisindolylmaleimide VIII (BIM-8) with DMPK.

Main Methods:

  • X-ray crystallography was used to determine the structure of the DMPK kinase domain bound to BIM-8.
  • Comparative structural analysis was performed with related kinases like Rho-associated kinases.

Main Results:

  • The crystal structure revealed a dimeric DMPK kinase domain associated via a conserved dimerization domain.
  • The kinase domain adopts an active conformation, with key catalytic residues properly positioned.
  • The inhibitor BIM-8 binds to the ATP site, showing a similar mode to PDK1.
  • Stable in vivo dimer formation likely requires the coiled-coil domains, not solely the kinase domain.

Conclusions:

  • The kinase domain alone is insufficient for stable DMPK dimerization in vivo.
  • The coiled-coil domains are essential for the stable formation of DMPK dimers.
  • The structural insights provide a basis for understanding DMPK function and inhibitor design.

More Related Videos

Modeling Myotonic Dystrophy 1 in C2C12 Myoblast Cells09:39

Modeling Myotonic Dystrophy 1 in C2C12 Myoblast Cells

Published on: July 29, 2016

Implantation of Osmotic Pumps and Induction of Stress to Establish a Symptomatic, Pharmacological Mouse Model for DYT/PARK-ATP1A3 Dystonia10:41

Implantation of Osmotic Pumps and Induction of Stress to Establish a Symptomatic, Pharmacological Mouse Model for DYT/PARK-ATP1A3 Dystonia

Published on: September 12, 2020

Related Concept Videos

The Sarcomere01:08

The Sarcomere

A sarcomere is a microscopic segment repeating in a myofibril. The sarcomere fundamentally consists of two main myofilaments: thick filaments called myosin and thin filaments called actin. These filaments interact by sliding past each other in response to stimulus. In addition to myosin and actin, several other proteins, such as tropomyosin, troponin, titin, nebulin, myomesin, α-actinin, and dystrophin, play crucial roles in regulating, structuring, and functioning of the sarcomere.
Each myosin...
Satellite Stem Cells and Muscular Dystrophy01:21

Satellite Stem Cells and Muscular Dystrophy

Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
Overview of Myosin Structure and Function01:15

Overview of Myosin Structure and Function

Myosins are a family of molecular motor proteins, first identified in the skeletal muscles, where they are responsible for muscle contraction. Along with their role in muscle contraction, these proteins also play a role in the intracellular transport of molecules and vesicles. There are twenty-four classes of myosins based on their domain sequence and organization. Of the twenty-four, six classes (Myosin I, Myosin II, Myosin V, Myosin VI, Myosin VII, and Myosin X)  have been well characterized.
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
ATP Synthase: Structure01:18

ATP Synthase: Structure

ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...