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与触珠蛋白-血红蛋白结合的人CD163的冷冻电镜结构揭示了血红蛋白清除的分子机制。

The Cryo-EM structure of human CD163 bound to haptoglobin-hemoglobin reveals molecular mechanisms of hemoglobin scavenging.

作者信息

Etzerodt Anders, Mikkelsen Jakob Hauge, Torvund-Jensen Morten, Hennig Dorle, Boesen Thomas, Graversen Jonas Heilskov, Moestrup Søren Kragh, Kollman Justin M, Andersen Christian Brix Folsted

机构信息

Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.

Inflammation Research, Department of Molecular Medicine, University of Southern Denmark, 5000, Odense C, Denmark.

出版信息

Nat Commun. 2024 Dec 30;15(1):10871. doi: 10.1038/s41467-024-55171-4.

DOI:10.1038/s41467-024-55171-4
PMID:39738064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11685794/
Abstract

CD163, a macrophage-specific receptor, plays a critical role in scavenging hemoglobin released during hemolysis, protecting against oxidative effects of heme iron. In the bloodstream, hemoglobin is bound by haptoglobin, leading to its immediate endocytosis by CD163. While haptoglobin's structure and function are well understood, CD163's structure and its interaction with the haptoglobin-hemoglobin complex have remained elusive. Here, we present the cryo-electron microscopy structure of the entire extracellular domain of human CD163 in complex with haptoglobin-hemoglobin. The structure reveals that CD163 assembles into trimers (and to some extent dimers), binding haptoglobin-hemoglobin in their center. Key acidic residues in CD163 interact with lysine residues from both haptoglobin and hemoglobin. Calcium-binding sites located near the haptoglobin-hemoglobin interface in CD163 provide explanation for the calcium dependence of the interaction. Furthermore, we show that the interaction facilitating CD163 oligomerization mimics ligand binding and is also calcium dependent. This structural insight into CD163 advances our understanding of its role in hemoglobin scavenging as well as its broader relevance to structurally related scavenger receptors.

摘要

CD163是一种巨噬细胞特异性受体，在清除溶血过程中释放的血红蛋白、抵御血红素铁的氧化作用方面发挥着关键作用。在血液中，血红蛋白与触珠蛋白结合，进而被CD163立即内吞。虽然触珠蛋白的结构和功能已为人熟知，但CD163的结构及其与触珠蛋白-血红蛋白复合物的相互作用仍不清楚。在此，我们展示了与触珠蛋白-血红蛋白形成复合物的人CD163整个胞外域的冷冻电镜结构。该结构显示，CD163组装成三聚体（在一定程度上也形成二聚体），在其中心结合触珠蛋白-血红蛋白。CD163中的关键酸性残基与触珠蛋白和血红蛋白中的赖氨酸残基相互作用。CD163中位于触珠蛋白-血红蛋白界面附近的钙结合位点解释了这种相互作用对钙的依赖性。此外，我们表明促进CD163寡聚化的相互作用模拟配体结合，并且也是钙依赖性的。对CD163的这一结构洞察加深了我们对其在血红蛋白清除中的作用以及它与结构相关的清道夫受体更广泛相关性的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/14f980c85415/41467_2024_55171_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/c87a4165021c/41467_2024_55171_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/a38ef1f035f3/41467_2024_55171_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/0b7afb6d6717/41467_2024_55171_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/3a64c309a3c1/41467_2024_55171_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/9bdc5ceb2e47/41467_2024_55171_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/e8bb370a7ba4/41467_2024_55171_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/4d9281cad646/41467_2024_55171_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/876b375d3c4c/41467_2024_55171_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/14f980c85415/41467_2024_55171_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/c87a4165021c/41467_2024_55171_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/a38ef1f035f3/41467_2024_55171_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/0b7afb6d6717/41467_2024_55171_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/3a64c309a3c1/41467_2024_55171_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/9bdc5ceb2e47/41467_2024_55171_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/e8bb370a7ba4/41467_2024_55171_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/4d9281cad646/41467_2024_55171_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/876b375d3c4c/41467_2024_55171_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/582c/11685794/14f980c85415/41467_2024_55171_Fig9_HTML.jpg

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2
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Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2. Epub 2021 Jul 15.
3
Recognition of lipoproteins by scavenger receptor class A members.清道夫受体家族成员对脂蛋白的识别。
巨噬细胞清道夫受体CD163介导的触珠蛋白-血红蛋白清除机制的结构解析
PLoS Biol. 2025 Jul 11;23(7):e3003264. doi: 10.1371/journal.pbio.3003264. eCollection 2025 Jul.
J Biol Chem. 2021 Aug;297(2):100948. doi: 10.1016/j.jbc.2021.100948. Epub 2021 Jul 9.
4
Reactive Oxygen Species and Their Involvement in Red Blood Cell Damage in Chronic Kidney Disease.活性氧及其在慢性肾脏病红细胞损伤中的作用
Oxid Med Cell Longev. 2021 Feb 25;2021:6639199. doi: 10.1155/2021/6639199. eCollection 2021.
5
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J Biol Chem. 2020 Nov 13;295(46):15727-15741. doi: 10.1074/jbc.RA120.014690. Epub 2020 Sep 9.
6
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7
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Life Sci Alliance. 2020 Feb 25;3(4). doi: 10.26508/lsa.201900502. Print 2020 Apr.
8
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10
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