Identifying Highly Conserved and Unique Structural Elements in Myosin VI

Abstract

Myosin VI possesses multiple unique features and is the only myosin known to move toward the (−)-end of actin filaments. This study used sequence and structure analyses to identify residues that are specific for myosin VI. Comparing the amino acids within myosin VI as well as between myosin VI and other myosins, we identified a series of myosin VI residues in the head region that are not only highly conserved in myosin VI, but whose amino acids are also distinct from those of other myosins. The majority of these myosin VI-specific residues have never been examined or speculated for their functional roles in myosin VI. Many of these residues locate in or adjacent to the converter domain. Among these residues, M701, P444, and F763 were revealed as unique for myosin VI. To further identify the mechanistic roles of these residues, we computationally mutated these three residues and examined their effects on conformational equilibrium using molecular dynamics simulation. We found that within a short 50-ns simulation, the conformational equilibria of mutated M701 and F763 were significantly deviated from the original states, indicating their important roles in linking the converter domain and the motor domain in the prestroke structure, potentially critical for the special rotation angle of myosin VI.