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<p>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&#xa0;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 <sup>1</sup>H, <sup>15</sup>N, and <sup>13</sup>C nuclei for wild-type asymmetric PF4 tetramers using TROSY-based triple resonance NMR experiments. We also used N<sub>z</sub>-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.</p>

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Resonance assignments of asymmetric tetrameric platelet factor 4 (PF4)

  • 期刊论文

  • 发表日期：

    2025年9月8日

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  • 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

摘要

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.