The mesa trail and the interacting heads motif of myosin II

UMMS Affiliation

Division of Cell Biology and Imaging, Department of Radiology; Craig Lab

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Biochemistry | Biophysics | Cell Biology | Enzymes and Coenzymes | Musculoskeletal System


Myosin II molecules in the thick filaments of striated muscle form a structure in which the heads interact with each other and fold back onto the tail. This structure, the "interacting heads motif" (IHM), provides a mechanistic basis for the auto-inhibition of myosin in relaxed thick filaments. Similar IHM interactions occur in single myosin molecules of smooth and nonmuscle cells in the switched-off state. In addition to the interaction between the two heads, which inhibits their activity, the IHM also contains an interaction between the motor domain of one head and the initial part (subfragment 2, S2) of the tail. This is thought to be a crucial anchoring interaction that holds the IHM in place on the thick filament. S2 appears to cross the head at a specific location within a broader region of the motor domain known as the myosin mesa. Here, we show that the positive and negative charge distribution in this part of the mesa is complementary to the charge distribution on S2. We have designated this the "mesa trail" owing to its linear path across the mesa. We studied the structural sequence alignment, the location of charged residues on the surface of myosin head atomic models, and the distribution of surface charge potential along the mesa trail in different types of myosin II and in different species. The charge distribution in both the mesa trail and the adjacent S2 is relatively conserved. This suggests a common basis for IHM formation across different myosin IIs, dependent on attraction between complementary charged patches on S2 and the myosin head. Conservation from mammals to insects suggests that the mesa trail/S2 interaction plays a key role in the inhibitory function of the IHM.


IHM, Interacting heads motif, Mesa trail, Myosin II mesa, Myosin head, Subfragment 2

DOI of Published Version



Arch Biochem Biophys. 2019 Dec 13;680:108228. doi: 10.1016/j.abb.2019.108228. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

Archives of biochemistry and biophysics

Related Resources

Link to Article in PubMed

PubMed ID