色谱2024，Vol.42Issue(7)：623-631,9.DOI:10.3724/SP.J.1123.2024.04029
蛋白质N-磷酸化修饰富集方法进展
Progress in enrichment methods for protein N-phosphorylation
摘要
Abstract
Protein phosphorylation is one of the most common and important post-translational modifications that regulates almost all life processes.In particular,protein phosphorylation reg-ulates the development of major diseases such as tumors,neurodegenerative diseases,and dia-betes.For example,excessive phosphorylation of Tau protein can cause neurofibrillary tangles,leading to Alzheimer's disease.Therefore,large-scale methods for identifying protein phospho-rylation must be developed.Rapid developmentin efficient enrichment methods and biological mass spectrometry technologies have enabled the large-scale identification of low-abundance protein O-phosphorylation modifications in,allowing for a more thorough study of their biologi-cal functions.The N-phosphorylation modifications that occur on the side-chain amino groups of histidine,arginine,and lysine have recently received increased attention.For example,the biological function of histidine phosphorylation in prokaryotes has been well studied;this type of modification regulates signal transduction and sugar metabolism.Two mammalian pHis kina-ses(NME1 and NME2)and three pHis phosphatases(PHPT1,LHPP,and PGAM5)have been successfully identified using various biological methods.N-Phosphorylation is involved in multiple biological processes,and its functions cannot be ignored.However,N-phosphorylation is unstable under acidic and thermal conditions owing to the poor chemical stability of the P-N bond.Unfortunately,the current O-phosphorylation enrichment method,which relies on acidic conditions,is unsuitable for N-phosphorylation enrichment,resulting in a serious lag in the large-scale identification of protein N-phosphorylation.The lack of enrichment methods has also seriously hindered studies on the biological functions of N-phosphorylation.Therefore,the de-velopment of efficient enrichment methods that target protein N-phosphorylation is an urgent undertaking.Research on N-phosphorylation proteome enrichment methods is limited,hinde-ring functional research.Thus,summarizing such methods is necessary to promote further functional research.This article introduces the structural characteristics and reported biological functions of protein N-phosphorylation,reviews the protein N-phosphorylation modification en-richment methods developed over the past two decades,and analyzes the advantages and dis-advantages of each method.In this study,both antibody-based and nonantibody-dependent methods are described in detail.Owing to the stability of the molecular structure of histidine,the antibody method is currently limited to histidine phosphorylation enrichment research.Fu-ture studies will focus on the development of new enrichment ligands.Moreover,research on ligands will promote studies on other nonconventional phosphorylation targets,such as two acyl-phosphates(pAsp,pGlu)and S-phosphate(pCys).In summary,this review provides a detailed analysis of the history and development directions of N-phosphorylation enrichment methods.关键词
蛋白质N-磷酸化/生物功能/富集方法/综述Key words
protein N-phosphorylation/biological function/enrichment method/review分类
化学化工引用本文复制引用
江波,高博,魏淑娴,梁振,张丽华,张玉奎..蛋白质N-磷酸化修饰富集方法进展[J].色谱,2024,42(7):623-631,9.基金项目
国家重点研发计划(2022YFC3401204) （2022YFC3401204）
国家自然科学基金(22074140,22393931) （22074140,22393931）
中国科学院大连化物所创新基金(DICP I202316).National Key R&D Program of China(No.2022YFC3401204) （DICP I202316）
National Natural Science Foundation of China(Nos.22074140,22393931) （Nos.22074140,22393931）
Innovation Program of Science and Research from Dalian Institute of Chemical Physics,Chinese Academy of Sciences(No.DICP I202316). （No.DICP I202316）
