Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1 autophagy adapter.
Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1 autophagy adapter.
复制标题
通过p62/sqstm1自噬适配器对N端规则底物的降解机制的见解。
DOI：
10.1038/s41467-018-05825-x
复制
发表时间：
2018-08-17
影响因子：
16.6
通讯作者：
Song HK
中科院分区：
文献类型：
--
作者：
Kwon DH;Park OH;Kim L;Jung YO;Park Y;Jeong H;Hyun J;Kim YK;Song HK
P62/SQSTM1是关键的自噬适配蛋白，也是多细胞信号转导的中枢。最近有报道称，自噬和N端规则通路通过p62联系在一起。然而，降解底物的确切识别模式和自噬途径中p62的调控仍不清楚。在这里，我们介绍了p62的ZZ结构域与各种类型的1和2N-退化之间的复杂结构。ZZ结构域与N-降解物相互作用所采用的结合模式不同于经典的N-识别素。还确定了通过PB1结构域的寡聚可以控制与R-Bip底物的功能亲和力。出乎意料的是，我们发现p62的自寡聚和解离是pH依赖的。这些发现拓宽了我们对N-端规则通路的功能的理解，并为自噬通路中p62的调节提供了洞察力。自噬适配器p62/SQSTM1在选择性自噬中起关键作用，并识别N-端规则底物。在这里，作者通过求解p62ZZ-结构域在不同类型1和2降解的络合物中的结构，提供了对p62 N-末端规则底物识别的分子见解，并展示了p62的pH依赖的齐聚作用。
p62/SQSTM1 is the key autophagy adapter protein and the hub of multi-cellular signaling. It was recently reported that autophagy and N-end rule pathways are linked via p62. However, the exact recognition mode of degrading substrates and regulation of p62 in the autophagic pathway remain unknown. Here, we present the complex structures between the ZZ-domain of p62 and various type-1 and type-2 N-degrons. The binding mode employed in the interaction of the ZZ-domain with N-degrons differs from that employed by classic N-recognins. It was also determined that oligomerization via the PB1 domain can control functional affinity to the R-BiP substrate. Unexpectedly, we found that self-oligomerization and disassembly of p62 are pH-dependent. These findings broaden our understanding of the functional repertoire of the N-end rule pathway and provide an insight into the regulation of p62 during the autophagic pathway. The autophagy adapter p62/SQSTM1 plays a key role in selective autophagy and also recognizes N-end rule substrates. Here the authors provide molecular insights into p62 N-end rule substrate recognition by solving the structures of the p62 ZZ-domain in complex with various type 1 and type 2 degrons and also show the pH dependent oligomerization of p62.
登录
查看更多内容
DOI：
10.1073/pnas.1615455113
发表时间：
2016-11-22
影响因子：
11.1
作者：
Cohen-Kaplan, Victoria;Livneh, Ido;Ciechanover, Aaron
通讯作者：
Ciechanover, Aaron
影响因子：
16.8
作者：
Choi, Woo Suk;Jeong, Byung-Cheon;Song, Hyun Kyu
通讯作者：
Song, Hyun Kyu
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
21.3
作者：
Cha-Molstad, Hyunjoo;Sung, Ki Sa;Hwang, Joonsung;Kim, Kyoung A.;Yu, Ji Eun;Yoo, Young Dong;Jang, Jun Min;Han, Dong Hoon;Molstad, Michael;Kim, Jung Gi;Lee, Yoon Jee;Zakrzewska, Adriana;Kim, Su-Hyeon;Kim, Sung Tae;Kim, Sun Yong;Lee, Hee Gu;Soung, Nak Kyun;Ahn, Jong Seog;Ciechanover, Aaron;Kim, Bo Yeon;Kwon, Yong Tae
通讯作者：
Kwon, Yong Tae
p62/SQSTM1形成自噬降解的蛋白质聚集体，并对亨廷顿蛋白诱导的细胞死亡具有保护作用。
影响因子：
7.8
作者：
Bjorkoy, Geir;Lamark, Trond;Brech, Andreas;Outzen, Heidi;Perander, Maria;Overvatn, Aud;Stenmark, Harald;Johansen, Terje
通讯作者：
Johansen, Terje