LANDELA
Indlela entsha emisha eyakhiwe ithimba lesayensi e-Center for Genomic Regulation (CRG) e-Barcelona ithole ukuba khona 'kwezilawuli ezikude' ezilawula ukusebenza kwamaprotheni futhi ezingasetshenziswa njengezinhloso zokuzuza izidakamizwa ezisebenza ngempumelelo kakhudlwana. futhi isebenza kahle kuma-pathologies ahlukahlukene njengokuwohloka komqondo, umdlavuza kanye nezifo ezithathelwanayo.
Lezi 'zilawuli kude' zaziwa ngokwesayensi njengezingosi ze-allosteric. Lezi izilawuli ezikude ezikude nendawo yesenzo seprotheni, kodwa zinamandla okuyilawula noma ukuyilungisa", uJúlia Domingo, umbhali wokuqala wocwaningo, olushicilelwe ngoLwesithathu ephephabhukwini elithi "Nature". uchazele u-ABC. Futhi wengeza isifaniso: "Kunjengokungathi ngaleso silawuli kude ungakhanyisa futhi uvale isibani noma ulawule amandla okukhanya."
Kulesi simo lapho ihlose ukuvimba noma ukulawula umsebenzi wamaprotheni agcina umsebenzi wawo oshintshiwe ekuboshweni. Isibonelo, esimweni somdlavuza, amaprotheni athole ukuguqulwa komsebenzi wawo ashintshiwe, akwenza ngendlela engavamile futhi iseli likhula ngendlela engavamile. Ezimweni eziningi, azikho izidakamizwa ezingashintsha noma zivimbe lo msebenzi ongajwayelekile noma, uma zikhona, aziqondile futhi zikhishwa kwamanye amaprotheni asebenza ngokujwayelekile.
Ngokwesiko, abazingeli bezidakamizwa baklame ukwelashwa okuqondise indawo esebenzayo yephrotheni, indawo yayo encane ekhiqiza ukusabela kwamakhemikhali lapho okuhlosiwe kubopha khona. I-drawback yalezi zidakamizwa, eyaziwa ngokuthi izidakamizwa ze-orthosteric, ukuthi izindawo ezisebenzayo zamaprotheni amaningi zifana kakhulu futhi izidakamizwa zibophe futhi zivimbela amaprotheni amaningi ahlukene ngesikhathi esisodwa, ngisho nalawo asebenza ngokujwayelekile futhi awathakazelisi ukuwathinta, okuyinto kungabangela imiphumela emibi.
“Lapho wangena embonweni we-allosteria nekhono elinalo lokuklama izidakamizwa. Into ethokozisayo mayelana nezingosi ze-allosteric ukuthi ziqondile kakhulu kuphrotheni ngayinye. Uma lezi zindawo ze-allosteric zithola ingxenye yendawo yephrotheni lapho umuthi ungahlala khona, izocaciswa ngokwedlulele kuleyo phrotheni. Sizokwazi ukulangazelela imithi esebenza ngempumelelo,” kuphawula umcwaningi.
“Asigcini nje ngokuthola ukuthi lezi zindawo zokwelapha ziningi, kodwa kunobufakazi bokuthi zingaphathwa ngezindlela eziningi ezahlukene. Esikhundleni sokumane sizivule futhi sizivale, singakwazi ukulungisa umsebenzi wazo njenge-thermostat. Ngokombono wobunjiniyela, kufana nokuthi sishaye igolide, ngoba kusinika indawo enkulu yokuklama 'izidakamizwa ezihlakaniphile' eziya kokubi futhi zeqe okuhle", kuchaza u-André Faure, umcwaningi we-postdoctoral e-CRG. kanye nomlobi wokuqala we-athikili.
isithombe esinezinhlangothi ezintathu esibonisa iphrotheni yomuntu i-PSD95-PDZ3 ngemibono ehlukene. I-molecule iboniswa ibophezela endaweni esebenzayo ngokuphuzi. I-gradient yombala oluhlaza kuya kobomvu ikhombisa amasayithi e-allosteric okungenzeka - u-André Faure/ChimeraX
Kulokhu kutholakala, ithimba lisebenzise indlela elivumela ukuthi lithathe amaprotheni kanye nefomu lesistimu kanye nokuhlangana komhlaba wonke nawo wonke amasayithi. Ukwenza lokhu, bakhethe amaprotheni amabili amaningi kakhulu ku-proteome yethu yomuntu. “I-50% yendawo yamaprotheni inamandla e-allosteric. Indlela yethu yenza kube nokwenzeka ukwenza i-atlas yeziza ze-allosteric, engenza inqubo yokufuna izidakamizwa ezisebenzayo isebenze kahle kakhulu”, kuqinisekisa u-Júlia Domingo.
Ababhali bocwaningo bathuthukise indlela ebizwa nge-double-depth PCA (ddPCA), abayichaza ngokuthi "ukuhlolwa kwamandla okuhlukumeza." "Sephula izinto ngamabomu ngezindlela eziyizinkulungwane ezahlukene ukuze sakhe isithombe esiphelele sokuthi okuthile kusebenza kanjani," kuchaza uSolwazi we-ICREA Research uBen Lehner, uMdidiyeli wohlelo lwe-Systems Biology kwa-CRG kanye nombhali wocwaningo. “Kufana nokuthi uma usola ukuthi i-spark plug yimbi, kodwa esikhundleni sokubheka lokho, umakhenikha uzoyihlukanisa yonke imoto bese ebheka zonke izingxenye ngayinye ngayinye. Ngokuhlaziya izinto eziyizinkulungwane eziyishumi ngesikhathi esisodwa, sithola zonke izingcezu ezibaluleke ngempela.”
Okulandelayo, sisebenzisa ama-algorithms obuhlakani bokwenziwa ukuze sitolike imiphumela yelebhu.
Enye yezinzuzo ezinkulu zale ndlela, ngaphezu kokwenza lula inqubo edingekayo ukuze uthole iziza ze-allosteric, ukuthi iyindlela ethengekayo nefinyelelekayo yanoma iyiphi ilabhorethri yocwaningo emhlabeni. “Kudinga nje ukufinyelela kuma-reagents ayisisekelo ebhayoloji yamangqamuzana, ukufinyelela ku-DNA sequencer kanye nekhompyutha. Ngalezi zingxenye ezintathu, noma iyiphi ilabhorethri ezinyangeni ezi-2-3, enesabelomali esincane, ingakwazi ukwenza lokhu kuhlolwa kuphrotheni yentshisekelo abayifunayo”, kuqinisekisa uJúlia Domingo. Ithemba labacwaningi liwukuthi ososayensi bethu bazosebenzisa le nqubo ngokushesha nangokubanzi imephu yezindawo ze-allosteric zamaprotheni omuntu ngamunye ngamunye. “Uma sinedatha eyanele mhlawumbe ngolunye usuku singadlulela phambili futhi sibikezele ukusuka ekulandelaneni kwamaprotheni kuye ekusebenzeni. Sebenzisa le datha ukuyiqondisa njengezindlela zokwelapha ezingcono zokubikezela ukuthi ushintsho oluthile ephrotheni luzowohloka lube yisifo”, kuphetha umcwaningi.
