ATP hydrolysis by the proteasome regulatory complex PAN serves multiple functions in protein degradation
ATP hydrolysis by the proteasome regulatory complex PAN serves multiple functions in protein degradation
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DOI：
10.1016/s1097-2765(02)00775-x
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发表时间：
2003-01-01
期刊：
影响因子：
16
通讯作者：
Goldberg, AL
中科院分区：
文献类型：
--
作者：
Benaroudj, N;Zwickl, P;Goldberg, AL
为了阐明ATP在蛋白水解中的作用，我们研究了古细菌20 S蛋白酶体和PAN（蛋白酶体激活核苷酸酶）调节复合物，真核生物19 S ATP酶的同源物。PAN的ATP酶活性刺激类似的球状（GFPssrA）和未折叠（酪蛋白）基板，并通过ssrA识别肽。GFPssrA的变性不会加速其降解或消除对PAN和ATP的需求。在一个球状或未折叠底物分子的降解过程中，300-400个ATP分子被水解。20 S α亚基中的N-末端缺失导致底物进入通道的开放和无PAN的未折叠蛋白的快速降解;然而，即使在PAN催化的未折叠之后，球状GFPssrA的降解仍然需要PAN的ATP酶活性。因此，底物结合激活ATP水解，从而促进三个过程：底物解折叠、20 S中的门打开和蛋白质易位。
To clarify the role of ATP in proteolysis, we studied archaeal 20S proteasomes and the PAN (proteasome-activating nucleotidase) regulatory complex, a homolog of the eukaryotic 19S ATPases. PAN's ATPase activity was stimulated similarly by globular (GFPssrA) and unfolded (casein) substrates, and by the ssrA recognition peptide. Denaturation of GFPssrA did not accelerate its degradation or eliminate the requirement for PAN and ATP. During degradation of one molecule of globular or unfolded substrates, 300-400 ATP molecules were hydrolyzed. An N-terminal deletion in the 20S alpha subunits caused opening of the substrate-entry channel and rapid degradation of unfolded proteins without PAN; however, degradation of globular GFPssrA still required PAN's ATPase activity, even after PAN-catalyzed unfolding. Thus, substrate binding activates ATP hydrolysis, which promotes three processes: substrate unfolding, gate opening in the 20S, and protein translocation.