Cooperative assembly of p97 complexes involved in replication termination.
Cooperative assembly of p97 complexes involved in replication termination.
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DOI：
10.1038/s41467-022-34210-y
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发表时间：
2022-11-03
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
p97 ATP酶从不同的细胞结构中提取多聚泛素化蛋白，为蛋白酶体的破坏做准备。p97与Ufd 1-Np 14和多种UBA-UBX辅因子一起发挥功能，但p97复合物如何在泛素化底物上组装尚不清楚。为了解决这个问题，我们研究了p97在复制终止过程中被泛素化后如何分解CMG解旋酶。我们表明，p97 Ufd 1-Np 14募集到CMG需要UBA-UBX蛋白Ubxn 7，相反，稳定的Ubxn 7结合到CMG需要p97 Ufd 1-Np 14。这种协同组装涉及Ubxn 7、p97、Ufd 1-Npl 4和泛素之间的相互作用。另一个p97辅因子Faf 1部分补偿了Ubxn 7的丢失。令人惊讶的是，p97 Ufd 1-Npl 4-Ubxn 7和p97 Ufd 1-Npl 4-Faf 1也在未锚定的泛素链上协同组装。我们建议，合作和底物独立的识别泛素链允许p97识别无限数量的多聚泛素化蛋白，同时避免形成部分，无活性的复合物。本研究描述了p97 Ufd 1-Np 14和UBA-UBX蛋白Ubxn 7在复制终止过程中如何分解脊椎动物复制体，并为p97复合物如何与UBA-UBX蛋白在泛素化底物上组装提供了新的见解
The p97 ATPase extracts polyubiquitylated proteins from diverse cellular structures in preparation for destruction by the proteasome. p97 functions with Ufd1-Npl4 and a variety of UBA-UBX co-factors, but how p97 complexes assemble on ubiquitylated substrates is unclear. To address this, we investigated how p97 disassembles the CMG helicase after it is ubiquitylated during replication termination. We show that p97Ufd1-Npl4 recruitment to CMG requires the UBA-UBX protein Ubxn7, and conversely, stable Ubxn7 binding to CMG requires p97Ufd1-Npl4. This cooperative assembly involves interactions between Ubxn7, p97, Ufd1-Npl4, and ubiquitin. Another p97 co-factor, Faf1, partially compensates for the loss of Ubxn7. Surprisingly, p97Ufd1-Npl4-Ubxn7 and p97Ufd1-Npl4-Faf1 also assemble cooperatively on unanchored ubiquitin chains. We propose that cooperative and substrate-independent recognition of ubiquitin chains allows p97 to recognize an unlimited number of polyubiquitylated proteins while avoiding the formation of partial, inactive complexes. This study describes how p97Ufd1-Npl4 and the UBA-UBX protein Ubxn7 disassemble vertebrate replisomes during replication termination, and it provides novel insights into how p97 complexes assemble with UBA-UBX proteins on ubiquitylated substrates
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
3.7
作者：
Franz A;Ackermann L;Hoppe T
通讯作者：
Hoppe T
DOI：
10.1083/jcb.202009147
发表时间：
2021-08-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fan Y;Köberlin MS;Ratnayeke N;Liu C;Deshpande M;Gerhardt J;Meyer T
通讯作者：
Meyer T
DOI：
10.1080/15384101.2020.1860559
发表时间：
2021-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Chauhan AK;Li P;Sun Y;Wani G;Zhu Q;Wani AA
通讯作者：
Wani AA
影响因子：
16.6
作者：
Franz A;Pirson PA;Pilger D;Halder S;Achuthankutty D;Kashkar H;Ramadan K;Hoppe T
通讯作者：
Hoppe T