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For print media, Jaly 2,1993
ScientistsDetermine 3-D Structure of Myosin: a Muscle Protein Critical to Life
La Jolla, CA. July 2, L993-- In the culminationof a l0-year collaborativeeffort,
researchers
havedeterminedthe three-dimensional
structureof myosin, a muscleprotein
essentialfor breathing,movementand blood flow in humansand animals. Using x-raJ
crystallography,a techniquein which x-raysprobethe structureof crystalsof pure
protein, the scientistsdeterminedthe structure.ofa critical portion of myosin down to the
precisearrangementof its individual atoms. Their resultsare describedin two articles
in the July 2, 1993, issueof Science.
"Human motion, indeedthe breathof life, dependson the contractionof skeletal
muscle," saysDr. RichardLymn, Director of the MuscleBiology Branchof the National
Instinrteof Arthritis and Musculoskeletal
and Skin Diseases,which supportedmuch of
this research. Theseresults,he says,"further our understanding
of the inner workings
of the molecularmotorsresponsiblefor musclepower."
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Myosin is a "molecularmotor," harnessingchemicalenergyto generatemotion the way
an engineusesgasolineto makea car move. A secondprotein, actin, makesup the
"roadways"or "tracks" alongwhich the molecularmotorstravel. Found in all animals
as well as plantsand fungi, myosin and aetinpower diversetypesof movementranging
from the transportof substances
within individualcells, to cell division and contractions
of the heart and body muscle.
Myosin makesit possiblefor singlecells to move within the body, aiding processessuch
as blood clotting, wound healing and responseto infection. The energy required for this
is producedwhen myosinburnsa chemicalfuel, adenosinetriphosphate(ATP), which is
producedfrom the food we eat.
"The primary importanceof the findings reportedhere lies in our understandingof how
the moleculesin muscleuseenergyto produceforce and motion," saysDr. Lymn.
"Since motion is essentialto humanactivity and energybalanceis important for health,
thesestudiesare basicto understanding
both normalbody function and musculoskeletal
fitness."
The three-dimensional
structureof the portion of myosin that generatesmotion is
describedin an article by Dr. Ivan Raymentand his colleaguesat the University of
Wisconsin,Madison, and the RobertWood JohnsonMedical School,Piscataway,New
Jersey. This work is a significantadvancebecausemyosin hasmore complexfunctions
and is larger than most proteinsthat have been studiedby crystallographictechniques.
"It took almostsix yearsto work out a way to get good crystals;it took anotherthree
yearsto solvethe crystal strucfure," saysRayment. In fact, researchers
havebeen
trying to crystallizemyosin sincethe 1960s.
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In a secondarticle in the sameissue,this detailedpicture of myosin and a similar picture
of actin were combinedwith information obtainedby examiningmusclefilaments at very
high magnificationin an electronmicroscope."X-ray methodsgive us extremelydetailed
pictures of the individual muscle componentsbut provide no information about the way
in which the componentsfit togetherto form a musclefilament. This type of
informationis providedby electronmicroscopy.Takentogether,theseefforts are a big
step forward in allowing scientiststo understandhow muscles,including the heart,
function at the molecularlevel," accordingto Dr. RonaldMilligan, explainingthe
synergisticrelationshipof the two methodsusedin the work.
Milligan's group at The ScrippsResearchInstitutein La Jolla, Calif., togetherwith Dr.
KennethHolmes and colleaguesat the Max Planck Institute in Heidelberg, Germany,
collaboratedwith the researchers
at UniversiWof Wisconsinon this studv.
The result is a view of one stagein the interactionof the molecular motor and its track.
The work "setsforward a structural model of how chemicalenergy gets changedinto
movement,"saysRayment."Many detailsare still missingfrom the model but having
the crystal structureof myosin is exciting becauseit allowsus to test our model in future
studies. This will help us understandall processes
that usemyosin-based
motors."
The results of thesetwo papersfill a gap in understandingthe workings of molecular
motors and musclecontraction. Skeletalmuscle,the most studiedsite of myosin action,
has a highly orderedstructuremadeup of multiple repeatsof the basicunit, the
sarcomere.The contractilemachineryof the sarcomereconsistsof alternatingrows of
thin filaments containing actin and thick filaments containingmyosin. During
contraction, the portion of the myosin that sticks out from the thick filaments - the part
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Page4 .- ScientistsDetermine3-D Structureof Myosin
studiedin the papersdiscussedhere -- grabsonto a neighboringthin filament and pulls,
causingthe sarcomereto shorten. The motion of individual actin and myosin proteins
generatesforces that add up to producewhole body motion and strength.
Muscle function is essentialfor eating, breathing, moving and pumping blood through
the body. Laboratory studieson invertebrateshave shownthat seriousdefectsin the
contractileproteinsare lethal, and this is presumablytrue for humansas well. Some
rare diseases,suchas familial hypertrophiccardiomyopathy(FHCM) -- a heart condition
that is the leading causeof suddendeathin apparentlyhealthy, young athletes-- are
causedby defectsin myosin.
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