Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes.
Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes.
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DOI：
10.1186/1472-6807-8-26
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发表时间：
2008-05-16
影响因子：
--
通讯作者：
Misra S
中科院分区：
文献类型：
--
作者：
Xu Z;Kohli E;Devlin KI;Bold M;Nix JC;Misra S
泛素(E3)连接酶与特定的泛素结合酶(E2)相互作用，泛化特定的底物蛋白。由于E2和E3的结合决定了泛素化的类型和生物学后果，因此了解E2：E3相互作用中的特异性基础是很重要的。E3连接酶芯片与Hsp70和Hsp90相互作用，泛素化由这些热休克蛋白陪伴的客户蛋白。CHIP与两种类型的E2酶UbcH5和UBC13-Uev1a相互作用。然而，尚不清楚为什么CHIP结合这些E2酶而不是其他酶，也不清楚CHIP是否优先与UbcH5或UBC13-Uev1a相互作用，这两种酶形成了不同类型的多泛素链。CHIP U-box结构域与UbcH5a络合的2.9ä晶体结构表明，ChIP通过类似的特异性决定因素与UbcH5和Ubc13结合，包括E2酶上的一个关键S-P-A基序。这些决定因素在CHIP和两种E2酶之间的整体相互作用中做出了不同的相对贡献。芯片经历UbcH5的自动泛素化，而不是UBC13-Uev1a。相反，CHIP通过UBC13-Uev1a驱动非锚定多泛素的形成。CHIP还与III型E2酶Ube2e2有效地相互作用，其中UbcH5和UBC13结合的特异性决定簇高度保守。芯片：UbcH5a结构强调了位于芯片U-box的长环和中央螺旋以及其同源E2酶的N端螺旋和环L4和L7上的特异性决定因素的重要性。S-P-A基序和其他特异性决定因素定义了CHIP的同源E2酶集合，其中可能包括几个III类E2酶。ChIP与UbcH5、Ube2e2和UBC13-Uev1a的相互作用与UBC13-Uev1a可能与其他E2酶顺序作用于K63连接的芯片底物的多泛素化的概念是一致的。
Ubiquitin (E3) ligases interact with specific ubiquitin conjugating (E2) enzymes to ubiquitinate particular substrate proteins. As the combination of E2 and E3 dictates the type and biological consequence of ubiquitination, it is important to understand the basis of specificity in E2:E3 interactions. The E3 ligase CHIP interacts with Hsp70 and Hsp90 and ubiquitinates client proteins that are chaperoned by these heat shock proteins. CHIP interacts with two types of E2 enzymes, UbcH5 and Ubc13-Uev1a. It is unclear, however, why CHIP binds these E2 enzymes rather than others, and whether CHIP interacts preferentially with UbcH5 or Ubc13-Uev1a, which form different types of polyubiquitin chains. The 2.9 Å crystal structure of the CHIP U-box domain complexed with UbcH5a shows that CHIP binds to UbcH5 and Ubc13 through similar specificity determinants, including a key S-P-A motif on the E2 enzymes. The determinants make different relative contributions to the overall interactions between CHIP and the two E2 enzymes. CHIP undergoes auto-ubiquitination by UbcH5 but not by Ubc13-Uev1a. Instead, CHIP drives the formation of unanchored polyubiquitin by Ubc13-Uev1a. CHIP also interacts productively with the class III E2 enzyme Ube2e2, in which the UbcH5- and Ubc13-binding specificity determinants are highly conserved. The CHIP:UbcH5a structure emphasizes the importance of specificity determinants located on the long loops and central helix of the CHIP U-box, and on the N-terminal helix and loops L4 and L7 of its cognate E2 enzymes. The S-P-A motif and other specificity determinants define the set of cognate E2 enzymes for CHIP, which likely includes several Class III E2 enzymes. CHIP's interactions with UbcH5, Ube2e2 and Ubc13-Uev1a are consistent with the notion that Ubc13-Uev1a may work sequentially with other E2 enzymes to carry out K63-linked polyubiquitination of CHIP substrates.
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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：
8
作者：
Kim, M;Tezuka, T;Yamamoto, T
通讯作者：
Yamamoto, T
影响因子：
21.3
作者：
Connell, P;Ballinger, CA;Patterson, C
通讯作者：
Patterson, C
影响因子：
4.8
作者：
Jiang, JH;Ballinger, CA;Patterson, C
通讯作者：
Patterson, C
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL