Prediction of a common structural scaffold for proteasome lid, COP9-signalosome and eIF3 complexes.
Prediction of a common structural scaffold for proteasome lid, COP9-signalosome and eIF3 complexes.
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DOI：
10.1186/1471-2105-6-71
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发表时间：
2005-03-24
影响因子：
3
通讯作者：
Hofmann K
中科院分区：
文献类型：
--
作者：
Scheel H;Hofmann K
26S蛋白酶体的“lid”亚复合物和COP9信号体（CSN复合物）共享一个共同的结构，由六个亚基组成，在它们的c端含有一个所谓的PCI结构域（蛋白酶体，CSN, eIF3），加上两个亚基含有MPN结构域（Mpr1/Pad1 n末端）。翻译起始复合物eIF3也含有PCI-和mpn结构域蛋白，但似乎偏离了6+2的化学计量。最初，PCI域被定义为上述成分之间可检测的序列相似性区域。在对蛋白酶体成分进行详尽的生物信息学分析时，我们在大多数PCI蛋白的n端区域检测到多个四联肽重复序列（TPR），这表明它们的同源性并不局限于PCI结构域。我们还在eIF3组分eIF3k中检测到一个以前未被识别的PCI结构域，该蛋白的3d结构最近才被确定。通过使用图谱引导比对技术，我们发现eIF3k中发现的结构元件很可能在所有PCI蛋白中都是保守的，从而得到了典型PCI结构域的结构模型。我们的模型预测同源结构域PCI在结构意义上不是一个真正的结构域，而是由两个子结构域组成：一个在PCI:PCI相互作用中起关键作用的c端“带翼螺旋”结构域，前面是一个螺旋重复区域。在PCI蛋白的n端区域检测到的tpr样重复序列很可能形成PCI结构域边界内重复序列的不间断延伸。这个模型可以解释几个令人困惑的实验结果。
The 'lid' subcomplex of the 26S proteasome and the COP9 signalosome (CSN complex) share a common architecture consisting of six subunits harbouring a so-called PCI domain (proteasome, CSN, eIF3) at their C-terminus, plus two subunits containing MPN domains (Mpr1/Pad1 N-terminal). The translation initiation complex eIF3 also contains PCI- and MPN-domain proteins, but seems to deviate from the 6+2 stoichiometry. Initially, the PCI domain was defined as the region of detectable sequence similarity between the components mentioned above. During an exhaustive bioinformatical analysis of proteasome components, we detected multiple instances of tetratrico-peptide repeats (TPR) in the N-terminal region of most PCI proteins, suggesting that their homology is not restricted to the PCI domain. We also detected a previously unrecognized PCI domain in the eIF3 component eIF3k, a protein whose 3D-structure has been determined recently. By using profile-guided alignment techniques, we show that the structural elements found in eIF3k are most likely conserved in all PCI proteins, resulting in a structural model for the canonical PCI domain. Our model predicts that the homology domain PCI is not a true domain in the structural sense but rather consists of two subdomains: a C-terminal 'winged helix' domain with a key role in PCI:PCI interaction, preceded by a helical repeat region. The TPR-like repeats detected in the N-terminal region of PCI proteins most likely form an uninterrupted extension of the repeats found within the PCI domain boundaries. This model allows an interpretation of several puzzling experimental results.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
影响因子：
14.9
作者：
Hulo, N;Sigrist, CJA;Bairoch, A
通讯作者：
Bairoch, A
影响因子：
14.9
作者：
Holm, L;Sander, C
通讯作者：
Sander, C
影响因子：
14.9
作者：
Bairoch, A;Apweller, R
通讯作者：
Apweller, R
影响因子：
64.8
作者：
Kellis, M;Patterson, N;Lander, ES
通讯作者：
Lander, ES