Muscle-type Creatine Kinase Interacts with Central Domains of the M-band Proteins Myomesin and M-protein

The sarcomeric cytoskeleton: from molecules to motion

“…Both myomesin and M-protein interact with creatine kinase around domains My6-My9, albeit with different affinities (Hornemann et al, 2003). Additional metabolic enzymes can be targeted to the M-band via FHL2, a member of the four and a half LIM-only protein family (Lange et al, 2002).…”

The M-band: an elastic web that crosslinks thick filaments in the center of the sarcomere

“…The invariant presence of myomesin at the M-band implies the presence of such a functional link in all types of vertebrate striated muscle. The M-band appearance depends probably on other factors, such as incorporation of the muscle isoform of creatine kinase (MM-CK) that appears electrondense in EM pictures [68,69]. The prominent M4 0 /M4 lines might result from the attachment of MM-CK to myomesin, while the varying M1 line is due to its binding to M-protein (see text).…”

“…Titin incorporation into the M-band network might also explain its role as a stress sensor in this region of the sarcomere (see below). Furthermore, the binding of the muscle isoform of creatine kinase (MM-CK) to myomesin domains My7-My8 [69] correlates with the M4 0 and M4 lines (Box 1). According to EM studies, these lines are of the same intensity in all muscles studied [21], which is consistent with the prominent expression of myomesin in all muscle types [26].…”

“…Similar to the PEVK fragment of titin, the EH-fragment is mostly unfolded and functions like an entropic spring [31] (Box 2). Phosphorylation sites (P, blue circles) [18,19] and interacting partners (identified above brackets) [11,18,30,69] are indicated.…”

SPR for molecular interaction analysis: a review of emerging application areas

“…SPR experiments downstream of yeast two hybrid screens (Hornemann et al, 2003;Hoffrogge et al, 2003;Wilkinson et al, 2003) and as one element in a systematic strategy for drug target identification (Oda et al, 2003) have been reported. The strategy for drug target identification involves purification of total binding proteins on drug matrixes, labeling with isotope coded affinity tag, proteolysis, identification of protein through liquid chromatography-mass spectrometry of peptides and finally confirmation of drug protein interactions with SPR.…”