ABSTRACT
These pioneering hypotheses did not receive wide approval, whereas there was a large consensus in favour of simple side-piece/cross-bridge models to account for force generation and active sliding in very different and innovative ways (A.F. Huxley 1957, 1965, 1969, 1971; Huxley and Simmons 1971, 1973). The cross-bridge theories were gradually modified and improved, from the conceptual, theoretical and semi-empirical points of view, by introducing, for instance, various experimental data, obtained over the years. These models are now described as swinging crossbridge/lever-arm processes and many detailed analyses and theories have been developed, concerning these mechanisms (e.g. Baker and Thomas 2000; Barclay 1999; Brenner 1990; Brenner and Eisenberg 1987; Brokaw 1995; Cooke 1986, 1995,
1997, 2004; Cooke et al. 1994; Duke 1999, 2000; Eisenberg and Hill 1978, 1985; Eisenberg et al. 1980; Fisher et al. 1995a; Geeves 1991; Geeves and Holmes 1999, 2005; Goldman and Huxley 1994; Hill 1968a,b, 1970, 1974, 1975, 1977; Hill and White 1968a,b; Hill et al. 1975; Holmes 1997; Holmes and Geeves 2000; Huxley 1973b,c; A.F. Huxley 1988, 2000; Huxley and Kress 1985; Huxley and Tideswell 1996, 1997; Irving 1987; Julian et al. 1978a; Linari et al. 2009; Ma and Zahalak 1991; Martyn et al. 2002; Mijailovich et al. 1996; Pate and Cooke 1989; Piazzesi and Lombardi 1995; Piazzesi et al. 2002b; Rayment et al. 1993a; Schoenberg 1980a,b, 1985; Smith and Mijailovich 2008; Smith et al. 2008; Squire 1983). A comment should be made regarding the remarkable experimental work and its interpretation (in terms of the mechanisms of muscle contraction, in particular) presented by Rayment et al. (1993a,b). Indeed, the authors resolved the atomic structure of the myosin subfragment-1 (S1 or head), using crystals of extensively methylated S1. Unfortunately, Phan et al. (1994) demonstrated that ‘methylation… causes a complete loss of in vitro motility of actin filaments over methylated HMM [heavy meromyosin, i.e. myosin subfragment containing the two heads, S1, plus the S2 part of myosin; see Figure 5.1 for definitions]… It is concluded that these relatively mild but numerous and important changes impair the function of methylated S1’. Thus, the promising work of Rayment et al. (1993a,b), which was seen as making a major contribution to our understanding of the myosin head, the head-actin interface and the molecular swinging cross-bridge/lever-arm mechanisms of muscle contraction, unfortunately seems to have been essentially a ‘non-event’ in terms of the mechanisms of muscle contraction.
