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  • 09월 01일 18시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제118회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Deletion of the N-terminus tail of alpha3 increases mammalian proteasome activity by “Open-Gate”

2016년 9월 1일 10시 04분 45초
BIO.P-155 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
10월 14일 (금요일) 11:00~12:30
저자 및
김선무, 최원훈, 이민재*
서울대학교 의과대학 생화학교실, Korea
Proteasomes degrade misfolded or damaged protein by proteolysis. The proteasome is the ~2.5 MDa holoenzyme complex consisting of two distinguishable the 19-subunit regulatory particle (RP, also known as the 19S) and the 28-subunit core particle (CP, also known as the 20S). CP is a cylindrical complex composed of four stacked rings. The internal two rings are made of seven beta-subunits (beta1-7) that contain catalytic sites. And the outer two rings are made of seven alpha-subunits (alpha1-7). The alpha-rings function as the “gate” when substrates enter to the barrel. When in the closed form, the axial substrate translocation channel of the CP is topologically blocked by the convergent N-termini of alpha subunits. To probe the role of channel gating in mammalian proteasomes, we have deleted the N-terminal tail of alpha 3. Here we show alpha3deltaN proteasomes are intact but hyperactive. It shows enhanced activity in three catalytic cites by measure the hydrolysis of fluorogenic peptide substrates. Polyubiquitinated Sic1 also showed enhanced degradation by purified alpha3deltaN proteasomes. Stable cells which are dominant negatively expressing the hyperactive proteasomes showed markedly elevated degradation of established proteasome substrates. And they were viable and highly resistant to oxidative stress. Potentially toxic proteins such as tau exhibited reduced accumulation and aggregate formation. These result provides that regulation of CP gate may function as the critical rate-limiting step in proteasomal degradation, and that opening the CP gate may be an effective strategy to reduce levels of aberrantly overexpressed or misfolded proteins in cells.