of the Max - MDC

Figure 1. 3D-model of the actomyosin complex. (A) Gauss–Connolly surfaces are used to
visualize the molecular complex. For clarity neighboring actin units are colored differently
(orange, brown, and yellow). The myosin comprises the S1 head (green), the regulatory
light chain (red), and the shortened essential light chain (white). In pink clusters of
acidic residues on actin (E361, D363, and E364) being identified as interaction sites for
the residues APKK at the N-terminus of S1(A1) are shown. Distances between Cα of D47
of the shortened essential light chain and Cα of E361 of actin are given in the table. The
modeled 46 N-terminal amino acids are depicted in blue. (B) More detailed view on the
potential interaction of N-terminal APKK of S1(A1) with acidic residues on actin. Ionic
interactions between lysine residues (K3 and K4) of APKK and acidic residues (E361 and
E364) on actin were assumed. The backbone of the 46 N-terminal residues are shown as
tube. The side chains of S1(A1) and E361, D363, and E364 are shown as cylinders.
Hydrogen atoms were omitted for clarity (from: Aydt et al. 2007).
Figure 2. Confocal images depicting the localization of ahnak-
C2 in the human heart. Longitudinal (A) and cross (B) sections
of human myocardium were stained for ahnak-C2 (green) and
nuclei (red). Ahnak-C2 labels the T-tubular system (small
arrows), the surface sarcolemma (star), and the intercalated
discs (big arrow) C) High magnification of a transversal section
showing one myocyte. The T-tubular system (arrows) is oriented
radially inside the myocyte (from: Hohaus et al. 2002, FASEB
16: 1205-1216).
Figure 3. Proposed model for sympathetic control of ICaL by ahnak/Ca 2+
channel binding. Left panel) Under basal conditions, ICaL carried by the
α1C-subunit is repressed by strong ahnak-C1/β2-subunit binding. Right
panel) Upon sympathetic stimulation, PKA sites in ahnak and/or in β2 become
phosphorylated. This releases the β2-subunit from tonic ahnak-C1 inhibition
resulting in increased ICaL. Hence, we propose ahnak-C1/β2-subunit binding
serves as physiological inhibitor of α1C conductance. Relief from this
inhibition is proposed as pathway used by the sympathetic signal cascade.
Likewise the missense mutation Ile5236Thr attenuated ahnak/β2 interaction
thus increasing ICaL. (from Haase et al., 2005).
Non-muscle myosins form the latch-bridges
Sustained activation of smooth muscle elicits an initial phasic
contraction, and a subsequent tonic contraction. Tonic
contraction of smooth muscle is unique, since it is generated
at almost basal free Ca 2+ , reduced oxygen consumption,
ATPase activity, and shortening velocity (“latch state”). The
latch mechanism remained obscure for decades. Smooth
muscle cells express three MyHC genes, namely one smoothmuscle-specific
(SM-MyHC) as well as two non-muscle-MyHC
(NM-MyHCA and NM-MyHCB). We eliminated expression of
the SM-MyHC by gene targeting technology. Smooth muscle
from knock-out neonatal mice did not exhibit initial phasic
contraction while tonic contraction remained normal.
Intracellular Ca 2+ transients of smooth muscle cells from
Cardiovascular and Metabolic Disease Research 39