A Chemical Proteomic Map of Heme-Protein Interactions.
A Chemical Proteomic Map of Heme-Protein Interactions.
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DOI：
10.1021/jacs.2c06104
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发表时间：
2022-08-24
影响因子：
15
通讯作者：
Parker, Christopher G.
中科院分区：
文献类型：
--
作者：
Homan, Rick A.;Jadhav, Appaso M.;Conway, Louis P.;Parker, Christopher G.
血红素是许多人类蛋白质的重要辅助因子，也是血液中氧气的主要转运体。最近的研究还确定血红素是一种信号分子，通过与蛋白质伙伴结合而不是通过其金属中心的反应性来发挥其作用。然而，人类蛋白质组中此类血红素结合蛋白的全面注释仍然不完整。在这里，我们描述了一种策略，利用基于血红素的光亲和探针与定量蛋白质组学相结合来绘制整个蛋白质组中血红素-蛋白质相互作用的图谱。在这些研究中，我们鉴定了 350 多种独特的血红素-蛋白质相互作用，其中绝大多数迄今为止未知，并且由不同功能类别的靶标组成，包括转运蛋白、受体、酶、转录因子和伴侣。这些蛋白质中包括免疫相关的白细胞介素受体相关激酶 1 (IRAK1)，我们提供了血红素激动其催化活性的初步证据。我们的研究结果应该可以提高目前对血红素调节及其信号功能的理解，并促进对其在人类疾病中的作用的新认识。
Heme is an essential cofactor for many human proteins as well as the primary transporter of oxygen in blood. Recent studies have also established heme as a signaling molecule, imparting its effects through binding with protein partners rather than through reactivity of its metal center. However, the comprehensive annotation of such heme-binding proteins in the human proteome remains incomplete. Here, we describe a strategy which utilizes a heme-based photoaffinity probe integrated with quantitative proteomics to map heme–protein interactions across the proteome. In these studies, we identified 350+ unique heme–protein interactions, the vast majority of which were heretofore unknown and consist of targets from diverse functional classes, including transporters, receptors, enzymes, transcription factors, and chaperones. Among these proteins is the immune-related interleukin receptor-associated kinase 1 (IRAK1), where we provide preliminary evidence that heme agonizes its catalytic activity. Our findings should improve the current understanding of heme’s regulation as well as its signaling functions and facilitate new insights of its roles in human disease.
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影响因子：
56.9
作者：
Cao, ZD;Henzel, WJ;Gao, XO
通讯作者：
Gao, XO
影响因子：
64.8
作者：
Galmozzi, Andrea;Kok, Bernard P.;Saez, Enrique
通讯作者：
Saez, Enrique
影响因子：
2.9
作者：
Bozinovic, Nina;Noe, Remi;Dimitrov, Jordan D.
通讯作者：
Dimitrov, Jordan D.
影响因子：
2.9
作者：
Fufezan, Christian;Zhang, Jun;Gunner, M. R.
通讯作者：
Gunner, M. R.
DOI：
10.1073/pnas.1905216116
发表时间：
2019-10-01
影响因子：
11.1
作者：
Freeman, Samuel L.;Kwon, Hanna;Raven, Emma L.
通讯作者：
Raven, Emma L.