ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins
ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins
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DOI：
10.1016/j.molcel.2005.10.019
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发表时间：
2005-12-09
期刊：
影响因子：
16
通讯作者：
Goldberg, AL
中科院分区：
文献类型：
--
作者：
Smith, DM;Kafri, G;Goldberg, AL
古细菌ATP酶复合物PAN是真核生物26 S蛋白酶体调节ATP酶的同源物，在ATP或ATP γ S结合时与20 S蛋白酶体瞬时结合，但不与ADP结合。通过电子显微镜（EM），PAN显示为双环结构，覆盖20 S，并且类似于19 S复合物中的两个密度。古细菌20 S α亚基的N末端被发现起着门的作用，阻止七残基肽的进入，但允许四肽的进入。在与20 S粒子缔合后，PAN刺激门打开。虽然球状蛋白的降解需要ATP水解，但PAN-20 S与ATP γ S的复合物转位并降解未折叠和变性的蛋白。兔26 S蛋白酶体也在ATP结合时降解这些未折叠的蛋白质，而不水解。因此，尽管解折叠需要来自ATP水解的能量，但仅ATP结合支持ATP酶-20S缔合、门打开和未折叠底物易位到蛋白酶体中，这可以通过ATP酶的促进扩散而发生。
The archaeal ATPase complex PAN, the homolog of the eukaryotic 26S proteasome-regulatory ATPases, was shown to associate transiently with the 20S proteasome upon binding of ATP or ATP gamma S, but not ADP. By electron microscopy (EM), PAN appears as a two-ring structure, capping the 20S, and resembles two densities in the 19S complex. The N termini of the archaeal 20S alpha subunits were found to function as a gate that prevents entry of seven-residue peptides but allows entry of tetrapeptides. Upon association with the 20S particle, PAN stimulates gate opening. Although degradation of globular proteins requires ATP hydrolysis, the PAN-20S complex with ATP gamma S translocates and degrades unfolded and denatured proteins. Rabbit 26S proteasomes also degrade these unfolded proteins upon ATP binding, without hydrolysis. Thus, although unfolding requires energy from ATP hydrolysis, ATP binding alone supports ATPase-20S association, gate opening, and translocation of unfolded substrates into the proteasome, which can occur by facilitated diffusion through the ATPase.