Muscle-type creatine kinase interacts with central domains of the M-band proteins myomesin and M-protein

J Mol Biol. 2003 Sep 26;332(4):877-87. doi: 10.1016/s0022-2836(03)00921-5.


Muscle-type creatine kinase (MM-CK) is a member of the CK isoenzyme family with key functions in cellular energetics. MM-CK interacts in an isoform-specific manner with the M-band of sarcomeric muscle, where it serves as an efficient intramyofibrillar ATP-regenerating system for the actin-activated myosin ATPase located nearby on both sides of the M-band. Four MM-CK-specific and highly conserved lysine residues are thought to be responsible for the interaction of MM-CK with the M-band. A yeast two-hybrid screen led to the identification of MM-CK as a binding partner of a central portion of myomesin (My7-8). An interaction was observed with domains six to eight of the closely related M-protein but not with several other Ig-like domains, including an M-band domain, of titin. The observed interactions were corroborated and characterised in detail by surface plasmon resonance spectroscopy (BiaCore). In both cases, they were CK isoform-specific and the MM-CK-specific lysine residues (K8. K24, K104 and K115) are involved in this interaction. At pH 6.8, the dissociation constants for the myomesin/MM-CK and the M-protein/MM-CK binding were in the range of 50-100 nM and around 1 microM, respectively. The binding showed pronounced pH-dependence and indicates a dynamic association/dissociation behaviour, which most likely depends on the energy state of the muscle. Our data propose a simple model for the regulation of this dynamic interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chickens
  • Connectin
  • Creatine Kinase / genetics
  • Creatine Kinase / metabolism*
  • Creatine Kinase, MM Form
  • Humans
  • Hydrogen-Ion Concentration
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Lysine / metabolism
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Point Mutation
  • Protein Binding
  • Protein Structure, Tertiary
  • Two-Hybrid System Techniques


  • Connectin
  • Isoenzymes
  • Muscle Proteins
  • Creatine Kinase
  • Creatine Kinase, MM Form
  • Lysine