脂质磷脂酸磷酸酶:结构、功能、调节和疾病关联。

Q1 Biochemistry, Genetics and Molecular Biology
Franceine S Welcome, Taisha C M Elizaire, Michael V Airola
{"title":"脂质磷脂酸磷酸酶:结构、功能、调节和疾病关联。","authors":"Franceine S Welcome, Taisha C M Elizaire, Michael V Airola","doi":"10.1016/j.jbior.2025.101082","DOIUrl":null,"url":null,"abstract":"<p><p>Lipids play essential roles as structural barriers in cell membranes, long-term energy storage, and as signaling molecules. One class of enzymes involved in lipid synthesis are lipins. Lipins are magnesium-dependent phosphatidic acid phosphatases that produce diacylglycerol, playing key roles in TAG synthesis, de novo phospholipid synthesis and metabolism. Here, we review recent advances on the structure, function, and regulation of lipins with a particular focus on the structural impacts of missense mutations associated with rhabdomyolysis, Majeed syndrome and neuropathies. Structural insights reveal that while some disease-associated mutations directly disrupt catalysis, many missense mutations are not near the active site, but still play a key role in PAP activity. With the resolved crystal structure of a lipin homolog Tt Pah2, AlphaFold, and AlphaMissense it has become increasingly possible to predict the pathogenicity and structural contributions of individual residues and mutations. Going forward, this structural information can be used to predict and understand new mutations as they arise.</p>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101082"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lipin phosphatidic acid phosphatases: Structure, function, regulation, and disease association.\",\"authors\":\"Franceine S Welcome, Taisha C M Elizaire, Michael V Airola\",\"doi\":\"10.1016/j.jbior.2025.101082\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Lipids play essential roles as structural barriers in cell membranes, long-term energy storage, and as signaling molecules. One class of enzymes involved in lipid synthesis are lipins. Lipins are magnesium-dependent phosphatidic acid phosphatases that produce diacylglycerol, playing key roles in TAG synthesis, de novo phospholipid synthesis and metabolism. Here, we review recent advances on the structure, function, and regulation of lipins with a particular focus on the structural impacts of missense mutations associated with rhabdomyolysis, Majeed syndrome and neuropathies. Structural insights reveal that while some disease-associated mutations directly disrupt catalysis, many missense mutations are not near the active site, but still play a key role in PAP activity. With the resolved crystal structure of a lipin homolog Tt Pah2, AlphaFold, and AlphaMissense it has become increasingly possible to predict the pathogenicity and structural contributions of individual residues and mutations. Going forward, this structural information can be used to predict and understand new mutations as they arise.</p>\",\"PeriodicalId\":7214,\"journal\":{\"name\":\"Advances in biological regulation\",\"volume\":\" \",\"pages\":\"101082\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-02-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in biological regulation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jbior.2025.101082\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in biological regulation","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.jbior.2025.101082","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0

摘要

脂质作为细胞膜的结构屏障、长期能量储存和信号分子发挥着重要作用。参与脂质合成的一类酶是脂质酶。脂质是镁依赖性磷脂酸磷酸酶,产生二酰基甘油,在TAG合成、新生磷脂合成和代谢中起关键作用。在这里,我们回顾了最近在脂质结构、功能和调控方面的进展,特别关注与横纹肌溶解、马吉德综合征和神经病变相关的错义突变的结构影响。结构洞察揭示,虽然一些疾病相关突变直接破坏催化,但许多错义突变不在活性位点附近,但仍在PAP活性中发挥关键作用。随着脂质同源物Tt Pah2、AlphaFold和AlphaMissense的晶体结构的解析,预测单个残基和突变的致病性和结构贡献变得越来越可能。展望未来,这些结构信息可以用来预测和理解新突变的出现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Lipin phosphatidic acid phosphatases: Structure, function, regulation, and disease association.

Lipids play essential roles as structural barriers in cell membranes, long-term energy storage, and as signaling molecules. One class of enzymes involved in lipid synthesis are lipins. Lipins are magnesium-dependent phosphatidic acid phosphatases that produce diacylglycerol, playing key roles in TAG synthesis, de novo phospholipid synthesis and metabolism. Here, we review recent advances on the structure, function, and regulation of lipins with a particular focus on the structural impacts of missense mutations associated with rhabdomyolysis, Majeed syndrome and neuropathies. Structural insights reveal that while some disease-associated mutations directly disrupt catalysis, many missense mutations are not near the active site, but still play a key role in PAP activity. With the resolved crystal structure of a lipin homolog Tt Pah2, AlphaFold, and AlphaMissense it has become increasingly possible to predict the pathogenicity and structural contributions of individual residues and mutations. Going forward, this structural information can be used to predict and understand new mutations as they arise.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Advances in biological regulation
Advances in biological regulation Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
8.90
自引率
0.00%
发文量
41
审稿时长
17 days
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信