Don haka menene ainihin "nadewar furotin"?

Cutar sankarau ta COVID-19 ta haifar da matsaloli da yawa waɗanda masu kutse suka ji daɗin kai hari. Daga 3D bugu na garkuwar fuska da abin rufe fuska na likitanci zuwa maye gurbin cikakken injin injin, kwararar ra'ayoyin ya kasance mai ban sha'awa da dumin zuciya. A lokaci guda, an yi ƙoƙarin ci gaba a wani yanki: a cikin bincike da nufin yaƙar cutar da kanta.

A bayyane yake, mafi girman yuwuwar dakatar da bala'in da ake fama da shi a halin yanzu da kuma wuce gona da iri ya ta'allaka ne kan hanyar da ke ƙoƙarin isa ga tushen matsalar. Wannan tsarin "san maƙiyin ku" ana ɗaukar shi ta hanyar Folding@Home computing project. Miliyoyin mutane sun sanya hannu kan aikin kuma suna ba da gudummawar wasu ikon sarrafa na'urorin sarrafa su da GPUs, don haka ƙirƙirar mafi girma [rabawa] supercomputer a tarihi.

Amma menene ainihin duk waɗannan exaflops ake amfani dasu? Me ya sa ya zama dole a jefa irin wannan ikon kwamfuta a furotin nadawa? Wane nau'in ilimin halitta ne ke aiki a nan, me yasa sunadaran suna buƙatar ninka kwata-kwata? Anan ga saurin bayyani game da nada furotin: menene, yadda yake faruwa, da dalilin da yasa yake da mahimmanci.

Na farko, abu mafi mahimmanci: me yasa ake buƙatar sunadarai?

Sunadaran sifofi ne masu mahimmanci. Ba wai kawai suna samar da kayan gini don sel ba, har ma suna aiki azaman masu haɓaka enzyme don kusan dukkanin halayen ƙwayoyin halitta. Squirrels, su ne tsari ko enzymatic, dogayen sarkoki ne amino acid, wanda ke cikin wani jeri. Ayyukan sunadaran suna ƙayyade ta abin da amino acid ke samuwa a wasu wurare akan furotin. Idan, alal misali, sunadaran suna buƙatar ɗaure ga ƙwayar cuta mai inganci, dole ne a cika wurin daurin da amino acid mara kyau.

Don fahimtar yadda sunadaran suna samun tsarin da ke kayyade aikinsu, muna buƙatar bincika tushen ilimin kwayoyin halitta da kwararar bayanai a cikin tantanin halitta.

Production, ko magana sunadaran suna farawa da tsari rubuce -rubuce. A lokacin rubutawa, DNA ɗin helix biyu, wanda ke ɗauke da bayanan kwayoyin halittar tantanin halitta, wani ɓangare na kwance, yana barin tushen nitrogen na DNA ya zama samuwa ga wani enzyme da ake kira. RNA polymerase. Aikin RNA polymerase shine yin kwafin RNA, ko kwafi, na kwayar halitta. Wannan kwafin kwayar halittar da ake kira manzo RNA (mRNA), kwayoyin halitta guda ɗaya ne manufa don sarrafa masana'antun furotin na ciki, ribosomeswadanda suka tsunduma cikin samarwa, ko watsa shirye-shirye sunadaran.

Ribosomes suna aiki kamar injunan taro - suna ɗaukar samfurin mRNA kuma suna daidaita shi da sauran ƙananan RNA, canja wurin RNA (tRNA). Kowane tRNA yana da yankuna biyu masu aiki - sashe na tushe uku da ake kira anticodon, wanda dole ne ya dace da madaidaicin codons na mRNA, da rukunin yanar gizo don ɗaure wani amino acid na musamman don wannan codon. A lokacin fassarar, ƙwayoyin tRNA a cikin ribosome suna ƙoƙarin ɗaure mRNA ta amfani da anticodons. Idan ya yi nasara, kwayoyin tRNA suna haɗa amino acid ɗin sa zuwa wanda ya gabata, yana samar da hanyar haɗin gwiwa ta gaba a cikin jerin amino acid ɗin da mRNA ke ɓoyewa.

Wannan jerin amino acid shine matakin farko na tsarin tsarin gina jiki, shi ya sa ake kiransa. tsarin farko. Gabaɗayan tsarin furotin mai girma uku da ayyukansa sun samo asali ne kai tsaye daga tsarin farko, kuma sun dogara da nau'ikan kaddarorin kowane amino acid da mu'amalarsu da juna. Ba tare da waɗannan kaddarorin sinadarai da hulɗar amino acid ba. polypeptides za su ci gaba da kasancewa jeri na layi ba tare da tsari mai girma uku ba. Ana iya ganin wannan a duk lokacin da kuka dafa abinci - a cikin wannan tsari akwai thermal denaturation uku-girma tsarin na sunadarai.

Tsawon dogon zangon sassan furotin

Matsayi na gaba na tsari mai girma uku, wanda ya wuce na farko, an ba shi suna mai wayo tsarin sakandare. Ya haɗa da haɗin gwiwar hydrogen tsakanin amino acid na aiki na kusa. Babban jigon waɗannan hulɗar daidaitawa ya zo ne zuwa abubuwa biyu: alpha helice и lissafin beta. Helix ɗin alpha yana samar da yanki mai naɗe sosai na polypeptide, yayin da takardar beta ta samar da santsi, yanki mai faɗi. Dukansu gyare-gyaren biyun suna da kaddarorin tsari da na aiki, dangane da halayen amino acid ɗin su. Misali, idan alpha helix ya ƙunshi galibi na amino acid hydrophilic, kamar arginine ko lysine, to zai fi dacewa ya shiga cikin halayen ruwa.

Alpha helices da beta zanen gado a cikin sunadaran. Abubuwan haɗin hydrogen suna samuwa a lokacin bayyanar furotin.

Wadannan sifofi guda biyu da haduwarsu sun zama mataki na gaba na tsarin gina jiki - tsarin jami'a. Ba kamar sassauƙan ɓangarorin tsarin sakandare ba, tsarin manyan makarantu ya fi tasiri ta hanyar hydrophobicity. Cibiyoyin yawancin sunadaran sun ƙunshi amino acid hydrophobic sosai, kamar alanin ko methionine, kuma an cire ruwa daga wurin saboda yanayin "mai laushi" na masu tsattsauran ra'ayi. Wadannan sifofi sukan bayyana a cikin sunadaran transmembrane da aka saka a cikin membrane bilayer na lipid da ke kewaye da sel. Yankunan hydrophobic na sunadaran suna dawwama cikin kwanciyar hankali a cikin ɓangaren mai mai na membrane, yayin da yankuna na hydrophilic na furotin suna fuskantar yanayin ruwa a bangarorin biyu.

Har ila yau, an tabbatar da kwanciyar hankali na tsarin manyan makarantu ta hanyar dogon zango tsakanin amino acid. Misali na yau da kullun na irin waɗannan haɗin gwiwa shine disulfide gada, sau da yawa faruwa tsakanin biyu cysteine ​​radicals. Idan kun ji warin wani abu kaɗan kamar ruɓaɓɓen qwai a cikin salon gashi yayin aiwatar da perm akan gashin abokin ciniki, to wannan wani yanki ne na denaturation na tsarin manyan keratin da ke cikin gashi, wanda ke faruwa ta hanyar rage haɗin disulfide tare da taimako na sulfur-dauke da thiol cakuda.

An daidaita tsarin manyan makarantu ta hanyar hulɗar dogon zango kamar hydrophobicity ko haɗin disulfide.

Disulfide bond na iya faruwa tsakanin cysteine masu tsattsauran ra'ayi a cikin sarkar polypeptide guda ɗaya, ko tsakanin cysteines daga cikakken sarƙoƙi daban-daban. Ma'amala tsakanin sarƙoƙi daban-daban suna samuwa na kwata matakin tsarin gina jiki. Kyakkyawan misali na tsarin quaternary shine haemoglobin yana cikin jinin ku. Kowane kwayoyin haemoglobin ya ƙunshi globins iri ɗaya guda huɗu, sassan furotin, kowannensu yana riƙe da takamaiman matsayi a cikin polypeptide ta gadojin disulfide, kuma yana da alaƙa da kwayar heme mai ɗauke da ƙarfe. Dukkan globins guda huɗu suna haɗe ta hanyar gadoji na intermolecular disulfide, kuma gabaɗayan kwayoyin suna ɗaure ga ƙwayoyin iska da yawa a lokaci ɗaya, har zuwa huɗu, kuma yana iya sakin su idan an buƙata.

Tsarin tsari don neman maganin cututtuka

Sarƙoƙin polypeptide sun fara ninkawa zuwa siffarsu ta ƙarshe yayin fassarar, yayin da sarkar girma ke fita daga ribosome, kamar yanki na ƙwaƙwalwar ƙarfe-alloy waya na iya ɗaukar sifofi masu rikitarwa lokacin zafi. Koyaya, kamar koyaushe a cikin ilimin halitta, abubuwa ba su da sauƙi haka.

A cikin sel da yawa, ƙwayoyin halittar da aka rubuta suna yin gyare-gyare mai yawa kafin fassarar, suna canza ainihin tsarin furotin idan aka kwatanta da tsantsar tushen jerin kwayoyin halitta. A wannan yanayin, hanyoyin fassara sau da yawa suna neman taimakon chaperones na kwayoyin halitta, sunadaran da ke ɗaure sarkar polypeptide na ɗan lokaci kuma suna hana shi ɗaukar kowane nau'i na tsaka-tsaki, wanda daga nan ba za su iya ci gaba zuwa na ƙarshe ba.

Wannan shine kawai a faɗi cewa tsinkayar sifar ƙarshe na furotin ba ƙaramin aiki bane. Shekaru da yawa, hanya daya tilo don nazarin tsarin sunadaran ita ce ta hanyoyin jiki irin su X-ray crystallography. Sai a ƙarshen 1960s masana kimiyyar halittu suka fara gina ƙirar ƙididdiga na nada furotin, da farko suna mai da hankali kan ƙirar tsarin na biyu. Waɗannan hanyoyin da zuriyarsu suna buƙatar bayanai masu yawa na shigarwa baya ga tsarin farko - alal misali, tebur na kusurwar kusurwoyi na amino acid, jerin abubuwan hydrophobicity, jahohin da aka caje, har ma da kiyaye tsari da aiki akan lokutan juyin halitta - duk don tunanin abin da zai faru yayi kama da furotin na ƙarshe.

Hanyoyin ƙididdigewa na yau don tsinkayar tsari na biyu, kamar waɗanda ke gudana akan hanyar sadarwa na Folding@Home, suna aiki tare da kusan 80% daidaito-wanda ke da kyau idan aka yi la'akari da sarkar matsalar. Bayanan da aka ƙirƙira ta samfuran tsinkaya akan sunadaran kamar sunadarin furotin na SARS-CoV-2 za a kwatanta su da bayanai daga nazarin jiki na ƙwayar cuta. A sakamakon haka, zai yiwu a sami ainihin tsarin gina jiki kuma, watakila, fahimtar yadda kwayar cutar ta danganta ga masu karɓa. Angiotensin yana canza enzyme 2 mutumin da ke cikin sashin numfashi wanda ke kaiwa cikin jiki. Idan za mu iya gano wannan tsari, za mu iya samun magungunan da ke toshe ɗaurin da kuma hana kamuwa da cuta.

Binciken nade-nadin sunadaran shine tushen fahimtarmu game da cututtuka da yawa da cututtuka waɗanda ko da mun yi amfani da hanyar sadarwa na Folding@Home don gano yadda za mu kayar da COVID-19, wanda muka gani yana fashe cikin haɓaka kwanan nan, hanyar sadarwar ta yi nasara' Kada ku yi aiki na dogon lokaci. Kayan aiki ne na bincike wanda ya dace sosai don nazarin tsarin sunadaran da ke haifar da yawancin cututtuka masu ɓarna sunadaran, irin su cutar Alzheimer ko cutar Creutzfeldt-Jakob, sau da yawa ba daidai ba ana kiranta cutar hauka. Kuma idan babu makawa wata kwayar cuta ta bayyana, za mu kasance a shirye don sake sake yakar ta.

source: www.habr.com