Resonance assignments of asymmetric tetrameric platelet factor 4 (PF4).

IF 0.6 4区生物学 Q4 BIOPHYSICS

Biomolecular NMR Assignments Pub Date : 2025-09-08 DOI:10.1007/s12104-025-10246-1

Qiulin Ma, Jinfeng Huang, Stephen Boulton, Ellen Mak, Madoka Akimoto, Estefanía López Giraldo, Mikayla Truong, Mercy Daka, Angela Huynh, Sarah Kwok, Rumi Clare, Ishac Nazy, Woonghee Lee, Giuseppe Melacini

{"title":"Resonance assignments of asymmetric tetrameric platelet factor 4 (PF4).","authors":"Qiulin Ma, Jinfeng Huang, Stephen Boulton, Ellen Mak, Madoka Akimoto, Estefanía López Giraldo, Mikayla Truong, Mercy Daka, Angela Huynh, Sarah Kwok, Rumi Clare, Ishac Nazy, Woonghee Lee, Giuseppe Melacini","doi":"10.1007/s12104-025-10246-1","DOIUrl":null,"url":null,"abstract":"Platelet Factor 4 (PF4), also known as CXCL4, is a CXC chemokine crucial for hemostasis, inflammation, and immune responses. Under physiological conditions PF4 assembles into asymmetric tetramers (31.2 kDa) that are dimers of dimers with highly flexible N-terminal regions. PF4 tetramers play a central role in prothrombotic autoimmune conditions, such as heparin-induced thrombocytopenia (HIT), as well as vaccine-induced immune thrombocytopenia and thrombosis (VITT). Here, we report the resonance assignments of 1H, 15N, and 13C nuclei for wild-type asymmetric PF4 tetramers using TROSY-based triple resonance NMR experiments. We also used Nz-exchange spectroscopy to identify peaks split by slow-exchange between two distinct conformational states caused by the asymmetry of PF4 tetramers. Our NMR assignments establish a foundation for future investigations into the structural dynamics and functional mechanisms of PF4 as well as its pathological role in anti-PF4 disorders.","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":" ","pages":""},"PeriodicalIF":0.6000,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomolecular NMR Assignments","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s12104-025-10246-1","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOPHYSICS","Score":null,"Total":0}

引用次数: 0

Abstract

Platelet Factor 4 (PF4), also known as CXCL4, is a CXC chemokine crucial for hemostasis, inflammation, and immune responses. Under physiological conditions PF4 assembles into asymmetric tetramers (31.2 kDa) that are dimers of dimers with highly flexible N-terminal regions. PF4 tetramers play a central role in prothrombotic autoimmune conditions, such as heparin-induced thrombocytopenia (HIT), as well as vaccine-induced immune thrombocytopenia and thrombosis (VITT). Here, we report the resonance assignments of ¹H, ¹⁵N, and ¹³C nuclei for wild-type asymmetric PF4 tetramers using TROSY-based triple resonance NMR experiments. We also used N_z-exchange spectroscopy to identify peaks split by slow-exchange between two distinct conformational states caused by the asymmetry of PF4 tetramers. Our NMR assignments establish a foundation for future investigations into the structural dynamics and functional mechanisms of PF4 as well as its pathological role in anti-PF4 disorders.

查看原文本刊更多论文

不对称四聚体血小板因子4 （PF4）的共振赋值。

血小板因子4 (PF4)，也称为CXCL4，是一种CXC趋化因子，对止血、炎症和免疫反应至关重要。在生理条件下，PF4组装成不对称四聚体（31.2 kDa），是具有高度柔性n端区域的二聚体的二聚体。PF4四聚体在血栓性自身免疫性疾病中发挥核心作用，如肝素诱导的血小板减少症（HIT），以及疫苗诱导的免疫性血小板减少症和血栓形成（VITT）。在这里，我们使用基于trosy的三重共振核磁共振实验报道了野生型不对称PF4四聚体的1H， 15N和13C核的共振分配。我们还使用nz -交换光谱来识别由于PF4四聚体的不对称导致的两种不同构象状态之间的缓慢交换而分裂的峰。我们的核磁共振任务为未来研究PF4的结构动力学和功能机制以及其在抗PF4疾病中的病理作用奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biomolecular NMR Assignments 生物-光谱学

CiteScore

1.70

自引率

11.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Biomolecular NMR Assignments provides a forum for publishing sequence-specific resonance assignments for proteins and nucleic acids as Assignment Notes. Chemical shifts for NMR-active nuclei in macromolecules contain detailed information on molecular conformation and properties. Publication of resonance assignments in Biomolecular NMR Assignments ensures that these data are deposited into a public database at BioMagResBank (BMRB; http://www.bmrb.wisc.edu/), where they are available to other researchers. Coverage includes proteins and nucleic acids; Assignment Notes are processed for rapid online publication and are published in biannual online editions in June and December.