Structural basis for TRIM72 oligomerization during membrane damage repair.
Structural basis for TRIM72 oligomerization during membrane damage repair.
复制标题
膜损伤修复过程中TRIM72寡聚化的结构基础。
DOI：
10.1038/s41467-023-37198-1
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发表时间：
2023-03-21
影响因子：
16.6
通讯作者：
Zhou, Chun
中科院分区：
文献类型：
--
作者：
Ma, Yuemin;Ding, Lei;Li, Zhenhai;Zhou, Chun
三方基序蛋白72（TRIM 72，也称为MG 53）通过膜融合和胞吐介导膜损伤修复。在损伤期间，TRIM 72分子响应于氧化环境形成分子间二硫键，并且TRIM 72寡聚体被提出将囊泡连接到质膜并与其他伴侣如dysferlin和caveolin一起促进膜融合。然而，TRIM 72寡聚化和作用的详细机制仍不清楚。在这里，我们提出了TRIM 72 B-box-coiled-coil-SPRY结构域（BCC-SPRY）的晶体结构，揭示了TRIM 72寡聚化的分子基础，这与二硫键的形成密切相关。通过结构导向突变，我们已经确定并表征了对TRIM 72的膜修复功能重要的关键残基。我们的研究结果还表明，TRIM 72与几种带负电荷的脂质，除了磷脂酰丝氨酸。我们的工作为进一步的机制研究以及TRIM 72的临床应用提供了结构基础。通过分子间二硫键的TRIM 72寡聚化对于细胞修复受损的膜是重要的。在这里，作者报道了TRIM 72二聚体的晶体结构，并表明TRIM 72 B盒二聚化促进TRIM 72寡聚化。
Tripartite Motif Protein 72 (TRIM72, also named MG53) mediates membrane damage repair through membrane fusion and exocytosis. During injury, TRIM72 molecules form intermolecular disulfide bonds in response to the oxidative environment and TRIM72 oligomers are proposed to connect vesicles to the plasma membrane and promote membrane fusion in conjunction with other partners like dysferlin and caveolin. However, the detailed mechanism of TRIM72 oligomerization and action remains unclear. Here we present the crystal structure of TRIM72 B-box-coiled-coil-SPRY domains (BCC-SPRY), revealing the molecular basis of TRIM72 oligomerization, which is closely linked to disulfide bond formation. Through structure-guided mutagenesis, we have identified and characterized key residues that are important for the membrane repair function of TRIM72. Our results also demonstrate that TRIM72 interacts with several kinds of negatively charged lipids in addition to phosphatidylserine. Our work provides a structural foundation for further mechanistic studies as well as the clinical application of TRIM72. TRIM72 oligomerization via intermolecular disulfide bonds is important for cells to repair damaged membranes. Here, authors report the crystal structure of TRIM72 dimer and show that TRIM72 B-box dimerization facilitates TRIM72 oligomerization.
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影响因子：
2.9
作者：
Dawidziak DM;Sanchez JG;Wagner JM;Ganser-Pornillos BK;Pornillos O
通讯作者：
Pornillos O
影响因子：
7.5
作者：
Han, Renzhi;Campbell, Kevin P.
通讯作者：
Campbell, Kevin P.
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：
3.8
作者：
Kim, Sunghyen;Seo, Jeonghwa;Park, Heonyong
通讯作者：
Park, Heonyong
影响因子：
17.1
作者：
Duann P;Li H;Lin P;Tan T;Wang Z;Chen K;Zhou X;Gumpper K;Zhu H;Ludwig T;Mohler PJ;Rovin B;Abraham WT;Zeng C;Ma J
通讯作者：
Ma J