Key result
Review maps cGKIα leucine zipper structures and myosin binding interactions via NMR and wenxiang diagrams.
Why the study?
The structural basis and interaction mechanisms of the leucine zipper coiled-coil domains of cGMP-dependent protein kinase Iα and myosin binding subunit of MLCP were not fully defined.
The use of wenxiang diagrams and NMR spectroscopy provides insights into the structural and functional mechanisms of protein-protein interactions involved in vascular smooth muscle relaxation.
Advances molecular understanding of vascular relaxation pathways; leaves open clinical translation pending functional validation.
Physiologic relaxation of vascular smooth muscle is induced by the cyclic guanosine monophosphate (cGMP)- dependent protein kinase Iα enzyme (cGKIα), which activates myosin phosphatase (MLCP). This activation process is thought to occur through the interaction involving both N- and C-terminal leucine zipper coiled-coil (LZCC) domains of the kinase enzyme (cGKIα) with the myosin binding subunit (MBS) of MLCP. In this review, I summarize how to define the LZCC domains in both N-terminal cGKIα1-59and C-terminal MBS proteins using predictive and experimental methods, how to make a rapid and accurate structure determination of a cGKIα1-59 molecule using NMR's residual dipolar coupling (RDC) measurements, and how to indentify the existence of a weak protein interaction between N-terminal LZCC domain (cGKIα1-59) and a LZCC domain (MBSCT42) within the C-terminal MBS. In addition, the location and orientation of the residues in LZCC proteins can be readily visualized using a novel diagram, the so-called “wenxiang diagram”, which is more advantageous than traditional helical wheel diagrams in analyzing LZCC protein structures and their action mechanisms. Using the composed wenxiang diagrams, we have characterized the interaction between cGKIα1- 59 and another LZCC molecule (MBSCT42), and deduced that the most affected residues of these two LZCC molecules might be at the positions d, a, e and g. These studies and findings are also covered in this review. It is intriguing to see that the successful incorporation of wenxiang diagrams and NMR spectroscopy in the LZCC structural and functional studies may provide some insights into protein-protein interaction mechanisms. Keywords: Coiled-coil, residual dipolar coupling, cGMP-dependent protein kinase, myosin binding subunit, NMR, wenxiang diagram, LZCC, MBSCT42, MLCP, RDC, PAIRCOIL, TROSY, HNCA, DTT, NOEsCoiled-coil, residual dipolar coupling, cGMP-dependent protein kinase, myosin binding subunit, NMR, wenxiang diagram, LZCC, MBSCT42, MLCP, RDC, PAIRCOIL, TROSY, HNCA, DTT, NOEs
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Guoping Zhou (2011) reported a review. This review summarizes the structural determination of the leucine zipper coiled-coil domains of cGKIα and its interaction with the myosin binding subunit using NMR and wenxiang diagrams.
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