白蛋白的完整C末端需要在人体内具有长的半衰期。,Communications Biology

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白蛋白的完整C末端需要在人体内具有长的半衰期。
Communications Biology ( IF 5.2 ) Pub Date : 2020-04-20 , DOI: 10.1038/s42003-020-0903-7
Jeannette Nilsen _{1,

2} , Esben Trabjerg ₃ , Algirdas Grevys _{1,

2} , Claudia Azevedo ₄ , Stephen O Brennan ₅ , Maria Stensland _{1,

6} , John Wilson ₇ , Kine Marita Knudsen Sand _{1,

8} , Malin Bern _{1,

2} , Bjørn Dalhus ₉ , Derry C Roopenian ₇ , Inger Sandlie _{1,

8} , Kasper Dyrberg Rand ₁₀ , Jan Terje Andersen _{1,

2}

Affiliation

Centre for Immune Regulation (CIR) and Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, Norway, Oslo, Norway.
Institute of Clinical Medicine and Department of Pharmacology, University of Oslo, Oslo, Norway.
Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
i3S, Instituto de Investigação e Inovação em Saúde, and Instituto de Engenharia Biomédica (INEB) and Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto and University of Porto, Porto, Portugal.
Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch Hospital, Christchurch, New Zealand.
Proteomics Core Facility, Oslo University Hospital Rikshospitalet, Oslo, Norway.
The Jackson Laboratory, Bar Harbor, ME, USA.
Department of Biosciences, University of Oslo, Oslo, Norway.
Department of Medical Biochemistry and Department for Microbiology, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway.
Protein Analysis Group, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.

白蛋白具有三周的平均血浆半衰期，因此是改善融合疗法的药代动力学的有吸引力的载体。半衰期由FcRn调节，FcRn是一种防止细胞内降解的细胞受体。为了量身设计白蛋白的治疗用途，了解白蛋白的结构变化如何影响FcRn结合和转运特性至关重要。在血液中，白蛋白的最后一个C末端残基（L585）可能会被酶切。在这里，我们证明去除L585残基会在主要FcRn结合结构域的区域引起结构稳定，并减少受体结合。与此相符，在急性胰腺炎患者中，缺乏L585的白蛋白裂解后的半衰期仅为3.5天。从而，

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更新日期：2020-04-24

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