Ïîëíàÿ âåðñèÿ ñòðàíèöû  English  

N-êîíöåâîé ìåòèîíèí – ñèãíàë äëÿ äåãðàäàöèè êëåòî÷íûõ áåëêîâ

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êàðòèíêà: N_met.pngÏîêàçàíî, ÷òî íàáîð N-êîíöåâûõ ñèãíàëîâ, óçíàâàåìûõ ñèñòåìàìè äåãðàäàöèè áåëêîâ, øèðå, ÷åì ñ÷èòàëîñü ðàíåå.  äîïîëíåíèå ê èçâåñòíûì ñèãíàëàì Arg/N- è Ac/N- ñèëüíûì ñèãíàëîì äåãðàäàöèè îêàçàëàñü ïîñëåäîâàòåëüíîñòü N-ìåòèîíèí ñ ïîñëåäóþùèì îñòàòêîì ãèäðîôîáíîé àìèíîêèñëîòû (Ô). Ýôôåêò MetΦ/N-êîíöà êàê ñèãíàëà äåãðàäàöèè ïðîäåìîíñòðèðîâàí êàê íà ñèíòåòè÷åñêèõ îëèãîïåïòèäàõ, òàê è íà ïðèðîäíûõ áåëêàõ in vivo.

Ïðàâèëî N-êîíöà äëÿ óáèêâèòèíèëèðîâàíèÿ è ïîñëåäóþùåé äåãðàäàöèè áåëêîâ áûëî ñôîðìóëèðîâàíî ãðóïïîé À. Âàðøàâñêîãî â 1986 ã. Â ñîîòâåòñòâèè ñ ýòèì ïðàâèëîì êîìïîíåíòû, îñóùåñòâëÿþùèå äåãðàäàöèþ (ðåêîãíèíû), óçíàþò N-êîíöåâûå ñèãíàëû äåãàäàöèè (äåãðîíû), è îñóùåñòâëÿþò ïîëèóáèêâèòèíèëèðîâàíèå áåëêà, ÷òî ïðèâîäèò ê åãî ðàñùåïëåíèþ ïðîòåîñîìàìè. Íåêîòîðûå N-êîíöåâûå àìèíîêèñëîòíûå îñòàòêè (Arg, Lys, His è äð.) ïðÿìî óçíàþòñÿ ðåêîãíèíàìè, äðóãèå (Asn, Gln, Asp è äð.) ïîäâåðãàþòñÿ äåçàìèäèðîâàíèþ, çàòåì àðãèíèëèðîâàíèþ è òàêàÿ ôîðìà óçíàåòñÿ ðåêîãíèíàìè. Åùå îäèí òèï ìîäèôèêàöèè äëÿ ïðèäàíèÿ ñâîéñòâà óçíàâàíèÿ ðåêîãíèíàìè ïðåäñòàâëÿåò ñîáîé àöåòèëèðîâàíèå N-êîíöà.

 ðàññìàòðèâàåìîé ðàáîòå àâòîðû ïîêàçàëè, ÷òî ñïåêòð äåãðîíîâ øèðå, ÷åì ñ÷èòàëîñü ðàíåå. Ýêñïåðèìåíòû ïðîâîäèëèñü íà óáèêâèòèí-ëèãàçå S. cerevisiae Ubr1, ñâÿçûâàþùåéñÿ ñ èììîáèëèçîâàííûìè íà ôèëüòðå îëèãîïåïòèäàìè. Îêàçàëîñü, ÷òî ðåêîãíèí Ubr1 ýôôåêòèâíî ñâÿçûâàåòñÿ ñ ïåïòèäàìè, â êîòîðûõ çà N-êîíöåâûì ìåòèîíèíîì ñëåäóåò ñèëüíî ãèäðîôîáíûé îñòàòîê Leu, Phe, Tyr, Trp èëè Ile (MetΦ/N ïåïòèäû). Àíàëîãè÷íûå ðåçóëüòàòû ïîëó÷åíû è äëÿ ìûøèíûõ Ubr1 è Ubr2. Îïðåäåëåí ñàéò Ubr1, óçíàþùèé äåãðîíû. Íåïðàâèëüíî óëîæåííûå áåëêè, íåñóùèå MetΦ/N äåãðîíû, ïîäâåðãàþòñÿ èíòåíñèâíîìó ðàñùåïëåíèþ.

 ýêñïåðèìåíòàõ íà S. ñerevisiaå, äåôåêòíûõ ïî ðàçëè÷íûì ðåêîãíèíàì, áûëî ïîêàçàíî, ÷òî ïðèðîäíûå áåëêè Msn4, Sry1, Arl3 è Pre5 â êëåòêå ìîãóò ïîäâåðãàòüñÿ äåãðàäàöèè ÷åðåç óçíàâàíèå èõ N-êîíöåâîãî ìåòèîíèíà.
àâòîðñêèé òåêñò

Ïîäïèñü ê ðèñóíêó: Ñïåöèôè÷åñêîå ñâÿçûâàíèå óáèêâèòèí-ëèãàçû S. cerevisiae Ubr1 ñ ïåïòèäàìè MZGSGAWLLP (Z = Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, Tyr).

Èñòî÷íèê: Kim HK, Kim RR, Oh JH, Cho H, Varshavsky A, Hwang CS. The N-terminal methionine of cellular proteins as a degradation signal. // Cell. 2014; V. 156: P. 158-169.
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