Myosin light chain kinase: functional domains and structural motifs

Publisher Website
Google Scholar
Abstract
Conventional myosin light chain kinase found in differentiated smooth and non‐muscle cells is a dedicated Ca2+/calmodulin‐dependent protein kinase which phosphorylates the regulatory light chain of myosin II. This phosphorylation increases the actin‐activated myosin ATPase activity and is thought to play major roles in a number of biological processes, including smooth muscle contraction. The catalytic domain contains residues on its surface that bind a regulatory segment resulting in autoinhibition through an intrasteric mechanism. When Ca2+/calmodulin binds, there is a marked displacement of the regulatory segment from the catalytic cleft allowing phosphorylation of myosin regulatory light chain. Kinase activity depends upon Ca2+/calmodulin binding not only to the canonical calmodulin‐binding sequence but also to additional interactions between Ca2+/calmodulin and the catalytic core. Previous biochemical evidence shows myosin light chain kinase binds tightly to actomyosin containing filaments. The kinase has low‐affinity myosin and actin binding sites in Ig‐like motifs at the N‐ and C‐terminus, respectively. Recent results show the N‐terminus of myosin light chain kinase is responsible for filament binding in vivo. However, the apparent binding affinity is greater for smooth muscle myofilaments, purified thin filaments, or actin‐containing filaments in permeable cells than for purified smooth muscle F‐actin or actomyosin filaments from skeletal muscle. These results suggest a protein on actin thin filaments that may facilitate kinase binding. Myosin light chain kinase does not dissociate from filaments in the presence of Ca2+/calmodulin raising the interesting question as to how the kinase phosphorylates myosin in thick filaments if it is bound to actin‐containing thin filaments.