简介：Majoradvanceshavebeenmadeoverthelastdecadeinourunderstandingofthemolecularbasisofseveralcardiacconditions.Hypertrophiccardiomyopathy(HCM)wasthefirstcardiacdisorderinwhichageneticbasiswasidentifiedandassuch,hasactedasaparadigmforthestudyofaninheritedcardiacdisorder.HCMcanresultinclinicalsymptomsrangingfromnosymptomstosevereheartfailureandprematuresuddendeath.HCMisthecommonestcauseofsuddendeathinthoseagedlessthan35years,includingcompetitiveathletes.Atleasttengeneshavenowbeenidentified,defectsinwhichcauseHCM.Allofthesegenesencodeproteinswhichcomprisethebasiccontractileunitoftheheart,i.e.thesarcomere.Whilemuchisnowknownaboutwhichgenescausediseaseandthevariousclinicalpresentations,verylittleisknownabouthowthesegenedefectscausedisease,andwhatfactorsmodifytheexpressionofthemutantgenes.StudiesinbothcellcultureandanimalmodelsofHCMarenowbeginningtoshedlightonthesignallingpathwaysinvolvedinHCM,andtheroleofbothenvironmentalandgeneticmodifyingfactors.Understandingthesemechanismswillultimatelyimproveourknowledgeofthebasicbiologyofheartmusclefunction,andwillthereforeprovidenewavenuesfortreatingcardiovasculardiseaseinman.

简介：ThemuscleproteinmyosinbindingproteinC(MyBPC)isalargemulti-domainproteinwhoseroleinthesarcomereiscomplexandnotyetfullyunderstood.MutationsinMyBPCarestronglyassociatedwiththeheartdiseasefamilialhypertrophiccardiomyopathy(FHC)andtheseexperimentsofnaturehaveprovidedsomeinsightintotheintricateworkingsofthisproteinintheheart.WhilesomeregionsoftheMyBPCmoleculehavebeenassignedafunctionintheregulationofmusclecontraction,theinteractionofotherregionswithvariouspartsofthemyosinmoleculeandthesarcomericproteins,actinandtitin,remainobscure.Inadditicn,severalintra-domaininteractionsbetweenadjacentMyBPCmoleculeshavebeenidentified.Althoughthebasicstructureofthemolecule(aseriesofimmunoglobulinandfibronectindomains)hasbeenelucidated,theassemblyofMyBPCinthesarcomereisatopicfordebate.ByanalysingtheMyBPCsequencewithrespecttoFHC-causingmutationsitispossibletoidentifyindividualresiduesorregionsofeachdomainthatmaybeimportanteitherforbindingorregulation.Thisreviewlooksatthecurrentliterature,inconcertwithalignmentsandthestructuralmodelsofMyBPC,inanattempttounderstandhowFHCmutationsmayleadtothediseasestate.