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palaeointensity database is still much too case that is far from closed, but tantalizing X-ray diffraction and electron microscopy4,
incomplete to test further any long-term support for their analysis comes from that suggested that the cross-bridge does not tilt
evolution in the geomagnetic moment. small, persistent quadrupole component as a whole but that part of the myosin head
The second possibility implies the exis- evident over the past 5 Myr. (called the ‘catalytic domain’ because it con-
tence of large supercontinents and their Jean-Pierre Valet and Yves Gallet are at the Institut tains a cleft into which ATP or ADP fits) is
migration towards low latitudes in response de Physique du Globe de Paris, 4 Place Jussieu, rigidly attached to the actin filament and that
to geoid anomalies, which could induce 75252 Paris Cedex 05, France. the part which acts as a lever is hinged to this
tumbling of the Earth with respect to the
rotation axis. The authors mention the
Rodinia supercontinent as a candidate
e-mail: valet@ipgp.jussieu.fr
1. Kent, D. V. & Smethurst, M. A. Earth Planet. Sci. Lett. 160,
391–402 (1998).
2. Hulot, G. & LeMouël, J.-L. Phys. Earth. Planet. Inter. 82,
domain. Although that report indicated that
the amount of relative movement between
the filaments generated by a working stroke
8
because it was assembled in the late Precam- 167–183 (1994).
would be only about 6 nm, too little to
brian and is supposed to have broken up 3. Quidelleur, X., Valet, J.-P., Courtillot, V. & Hulot, G. Geophys. account for the responses of intact muscle
between 750 and 600 Myr. They also men- Res. Lett. 21, 1639–1642 (1994). fibres to sudden shortening steps5, subse-
4. Johnson, C. L. & Constable, C. G. Geophys. J. Int. 122, 489–519
tion Pangaea, which was assembled during (1995).
quent X-ray analyses of crystals of myosin
the Palaeozoic. It would thus be interesting 5. Johnson, C. L. & Constable, C. G. Geophys. J. Int. 131, 643–666 fragments6,7 indicate a stroke of 10–12 nm.
to detect any relationship between the break- (1997). Together with about 2 nm contributed by the
up of these supercontinents and inclination 6. Carlut, J. & Courtillot, V. Geophys. J. Int. 134, 527–544 (1998). compliance of the filaments, this would
7. Evans, M. E. Nature 262, 676–677 (1976).
anomalies that would reflect a change in the 8. Piper, J. D. A. & Grant, S. Phys. Earth. Planet. Inter. 55, 37–53
explain the 13 nm taken up during the first
geoid linked to mass redistribution. (1989). few milliseconds after a quick release from
Kent and Smethurst have raised some fas- 9. McElhinny, M. W. & Lock, J. Surv. Geophys. 17, 557–591 (1996). isometric contraction5.
cinating issues about the early generation of 10. Stevenson, D. J., Spohn, T. & Schubert, G. Icarus 54, 466–489
Suzuki et al.1 describe experiments by
(1983).
the geomagnetic field and about the possible 11. Labrosse, S., Poirier, J.-P. & LeMouël, J.-L. Phys. Earth Planet. fluorescence resonance energy transfer
influences of the mantle on the field. This is a Inter. 99, 1–17 (1997). (FRET). Two fluorescent molecules are
attached to different points on myosin, and
Muscle the one working at the shorter wavelength
(the donor) is excited by light. The energy of
Support for the lever arm this excited state may transfer to the other
(the acceptor), which then emits a photon at
A. F. Huxley
its fluorescence wavelength. The extent of
this energy transfer varies inversely with the
n pages 380 and 383 of this issue, detach. Attachment ends when a molecule of sixth power of the distance between the two

O Suzuki et al.1 and Dobbie et al.2
describe investigations which sup-
port current ideas on the way in which
ATP binds to the myosin head. This ATP is
hydrolysed during the next cycle in steps,
some of which are coupled to conformation-
fluorophores and so is a sensitive indicator of
their separation.
Suzuki et al. used a myosin fragment con-
changes in the cross-bridges between the al changes in which the cross-bridge tilts, sisting of the catalytic domain together with
myosin and actin filaments of muscle gen- stretching an elastic component and thus the presumed hinge and the beginning of the
erate force or shortening. raising the tension. lever. The two fluorophores were attached on
Length changes in muscle take place by The only attempt so far at a detailed either side of the hinge, and the extent of
relative sliding of two overlapping sets of calculation of the molecular forces between energy transfer was measured without ATP
filaments, composed respectively of myosin myosin and actin3 suggested that there is a (end of the working stroke). On addition of
and actin. Tension is generated in the overlap sequence of positions of decreasing potential ATP, which causes the recovery stroke, ener-
regions by cross-bridges formed by the heads energy, and that the head as a whole tilts from gy transfer was much reduced. When myosin
of myosin molecules, which attach to an each position to the next. However, the in the absence of actin binds ATP, it rapidly
adjacent actin filament, exert force and structure of the myosin head, established by undergoes an isomerization after which the
ATP is hydrolysed to ADP and inorganic
a b phosphate, both of which remain bound
until the next working stroke. It follows that
Myosin filament
Thick filament the recovery stroke, indicated by the decrease
in energy transfer, accompanies or precedes
the actual hydrolysis step.
Lever arm
The authors also measured energy trans-
Actin fer in two mutant myosins. With one of these,
filament Catalytic domain
believed to hold the myosin in the state before
the isomerization, the energy transfer was
similar to that in rigor; but with the other, the
myosin was in the post-isomerization state
Figure 1 Presumed shape changes in a representative cross-bridge. a, During active contraction at and the energy transfer was similar to that of
fixed overall length; b, during rigor. Increase of length corresponds to displacement of the myosin the normal myosin with ATP (after the recov-
filament to the left. The muscle is being subjected to a length oscillation with 3-nm peak-to-peak ery stroke). Therefore the recovery stroke
amplitude of relative sliding of filaments; the red outlines show the situation at the maximum length accompanies the isomerization — that is, not
and the black outlines at the minimum. In a, the centre of mass of the lever arm is to the left of that of hydrolysis itself but the preceding step.
the catalytic domain, so that the contour of total mass of the cross-bridge is more spread out in the Calculated distances between donor and
stretched case (red) than when shortened (black), respectively decreasing and increasing the intensity acceptor agreed with the changes expected
of the X-ray reflection corresponding to the repeat of myosin molecules along the filament. The from the presumed rotation at the hinge. But
intensity therefore fluctuates in opposite phase to the length. In b, the situation is reversed (centre of the efficiency of fluorescence energy transfer
mass of the lever arm is to the right of that of the catalytic domain) and the intensity fluctuation is in depends on the relative orientations of the
phase with length. fluorophores as well as on their separation.
NATURE | VOL 396 | 26 NOVEMBER 1998 | www.nature.com Nature © Macmillan Publishers Ltd 1998 317
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These were unknown and, as is customary, muscle) from electron-paramagnetic-reso- Daedalus
Suzuki et al. took an averaged value for their nance spectra, a method that cannot distin-
effect on transfer efficiency. Their Fig. 4 guish between angles on the two sides of the Fat is a feminist issue
(page 382), however, shows that they assume perpendicular.
a large change in the relative angular posi- Dobbie et al. explain these X-ray intensity Fat causes a multitude of miseries these
tions of the two fluorophores during the changes quantitatively. In their model (Fig. days, mainly to women. Emaciation is
working stroke, so the estimated distances 3, page 385) the tip of the lever moves by intensely fashionable. The sub-text of this
are subject to uncertainty.
Using a variant of FRET, Getz et al.8 also
showed that the working stroke is accompa-
about 9 nm during the working stroke, a little
less than the 10–12 nm (suggested by X-ray
structures6,7) which matches the amount
fashion, says Daedalus, is sexual, but not
in the obvious way. Many cultures
consider obesity to be sexy; George Orwell
8
nied by a conformational change. The donor deduced from sudden length changes (see commented on the rotundity of the
was a molecule containing a terbium atom above). If this 9 nm turns out to be correct it Englishman’s secret ideal. This makes
which is luminescent rather than fluores- will therefore be necessary to postulate some good biological sense. Fat is itself a source
cent, making a combination that operates movement in addition to that from the swing of oestrogen, so fat women are likely to be
over greater separations than ordinary FRET of the lever, perhaps from tilting of the sexually enthusiastic — a fact celebrated
and has other advantages9. The fragment of catalytic domain on the actin filament3 or by a famous English cartoon duo.
myosin used included the catalytic domain shortening of the connection of the myosin Conversely, thin women should have a
and the whole of the lever. The donor was head to the shaft of its filament12. weaker sexual drive. Anorexic women
attached close to the tip of the lever and the All of this is impressive support for the often even cease to menstruate.
fluorescent acceptor to the catalytic domain; lever-arm hypothesis, but many questions So Daedalus reckons that fashionable
actin was present so rigor attachments were remain. How many of the myosin heads are slimness is really about power. A slim
formed. On adding ATP (myosin dissociates active at any one time? Is the working stroke woman hopes to arouse strong desire in
from actin and recovery stroke occurs), an a single event or does it go in two or more the opposite sex, while being immune to it
increase in transfer was found, although suf- steps? Answers may come from measure- herself — a position of great power. The
ficient change in separation between donor ments of the force and amount of movement age-old sex war, augmented by the modern
and acceptor would not be expected from the between a single myosin molecule and an feminist battle, therefore decrees that
presumed recovery stroke of the lever. Getz et actin filament. But the time resolution of slimness should be fashionable.
al. concluded that the decrease of transfer such experiments is inferior to that of experi- This unstated realpolitik of modern
was the result of a change in orientation of ments on whole fibres, the results are affect- fashion leaves fat women in a sorry plight.
the acceptor, although other explanations ed by compliance in the actin filaments, For not only does fat release sex hormones;
are possible. Their result is a timely warning and there are big discrepancies between sex hormones encourage fat to accumulate,
that FRET results do not unambiguously the results from different laboratories. in its usual sites around the female frame.
indicate a change in separation between Moreover, experiments are done with By positive feedback, a fat woman may get
donor and acceptor. myosins from different animals, and at low ever fatter, more sexually needy, but less
These observations1,8 confirm that a con- temperatures where the behaviour of the fashionably desirable. Meanwhile her slim
formational change within the myosin mol- intact muscle is unknown. sisters, sexually switched off by their
ecule does accompany the working stroke, Many will echo Holmes’s remark6: “The emaciation, can denounce men for
but do not indicate its extent. The results of fact that these results fit so nicely with other harassing them with unwanted attentions.
Dobbie et al.2 are complementary: they pro- experiments supporting the lever-arm Daedalus wants to break this vicious
vide a value for this extent without giving hypothesis points to their significance”. cycle. Many chemicals said to damage
further evidence for a conformational Perhaps so, but results that agree with animal reproduction (such as DDT)
change. An intact fibre from frog muscle was one’s preconceptions need to be scrutinized concentrate in body fat. So DREADCO
stimulated and a small length oscillation was with especial care. I readily admit that I am chemists are seeking a drug which
imposed at a frequency (about 3 kHz) too inclined to accept results that fit with a work- dissolves in the fat, but stimulates rather
high for the conformational changes to fol- ing stroke of at least 10 nm suggested long than sabotages its biochemistry. It must
low, so that the tension and length changes ago by experiments on living muscle5, rather boost not only the production of oestrogen
were in phase. The intensity of the meridion- than values in the 4–6 nm range that were (so that even women with little fat will feel
al X-ray reflection corresponding to the widely accepted a year ago13. sexy) but also leptin — the feedback-
spacing (14.5 nm) of myosin molecules A. F. Huxley is at Trinity College, Cambridge control protein which counters obesity by
along their filaments was also recorded and CB2 1TQ, UK. damping production of further fat. Arsenic
its fluctuations were exactly in opposite 1. Suzuki, Y., Yasunaga, T., Ohkura, R., Wakabayashi, T. & Sutoh, may give a clue; in low doses it can lead
phase to the length changes. However, when K. Nature 396, 380–383 (1998). both to emaciation and hypersexuality.
2. Dobbie, I. et al. Nature 396, 383–387 (1998).
a similar experiment was done on a fibre in 3. Diaz Baños, F. G., Bordas, J., Lowy, J. & Svensson, A. Biophys. J.
The biochemical development may be
rigor (that is, without ATP so that all cross- 71, 576–589 (1996). long and tortuous. But the final product
bridges were presumably in the state corre- 4. Rayment, I. et al. Science 261, 58–65 (1993). will splendidly counter the malign
sponding to the end of the stroke), the X-ray 5. Ford, L. E., Huxley, A. F. & Simmons, R. M. J. Physiol. 269, influence of modern fashion. With
441–515 (1977).
intensity fluctuations were exactly in phase 6. Holmes, K. C. Curr. Biol. 7, R112–R118 (1997).
DREADCO’s ‘Slim and Sexy’ fat-activator,
with the length changes. 7. Dominguez, R., Freyzon, Y., Trybus, K. M. & Cohen, C. Cell 94, fat women will shed their girth without
These results confirm those of Yagi et al.10 559–571 (1998). damping their ardour; slim women will no
at a lower frequency (500 Hz) where phase 8. Getz, E. B., Cooke, R. & Selvin, P. R. Biophys. J. 74, 2451–2458 longer sacrifice sexual feeling to fashion;
(1998).
shifts are appreciable. They imply that the 9. Selvin, P. R. & Hearst, J. E. Proc. Natl Acad. Sci. USA 91,
post-menopausal women building their
long axis of the cross-bridge swings from one 10024–10028 (1994). middle-age spread may not need HRT.
side to the other of the perpendicular to the 10. Yagi, N. et al. J. Synch. Rad. 3, 305–312 (1996). Militant feminists, of course, will find
fibre axis during a working stroke (Fig. 1). 11. Baker, J. E., Brust-Mascher, I., Ramachandran, S., LaConte, good reasons to avoid and denounce the
L. E. W. & Thomas, D. D. Proc. Natl Acad. Sci. USA 95,
This agrees with results from fluorescent 2944–2949 (1998).
product.
probes attached to the lever arm but con- 12. Harrington, W. F. Proc. Natl Acad. Sci. USA 68, 685–689 (1971). David Jones
tradicts a conclusion11 reached (on a scallop 13. Howard, J. Nature 389, 561–567 (1997).

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