Mapping the Proteoform Landscape of Five Human Tissues.
Mapping the Proteoform Landscape of Five Human Tissues.
复制标题
DOI：
10.1021/acs.jproteome.2c00034
复制
发表时间：
2022-05-06
影响因子：
4.4
通讯作者：
Kelleher, Neil L.
中科院分区：
文献类型：
--
作者：
Drown, Bryon S.;Jooss, Kevin;Melani, Rafael D.;Lloyd-Jones, Cameron;Camarillo, Jeannie M.;Kelleher, Neil L.
关键词：
对人体功能的理解需要大规模的蛋白质结构-功能研究。蛋白质的化学结构在转录、翻译和翻译后水平上受到控制，从而在细胞内产生具有调节功能的各种产物。术语“蛋白形式”在化学组成水平上封装了这种复杂性。要全面绘制人体组织中的蛋白质组图谱，就必须采用具有更高灵敏度和覆盖深度的分析技术。在这里，我们采取了自上而下的蛋白质组学方法，结合使用毛细管区带电泳（CZE）和纳米流反相液相色谱（RPLC）联用质谱法生成的数据，以识别和表征来自人类肺，心脏，脾脏，小肠和肾脏的蛋白质。CZE和RPLC提供了互补的翻译后修饰和蛋白质型选择性，从而在组合使用时提高了整体蛋白质组覆盖率。在本研究中鉴定的11，466种蛋白质型中，7373种（64%）以前未报告。蛋白质和蛋白质型水平的巨大差异很容易量化，初步推断蛋白质型生物学在分析的器官中起作用。防御素、谷胱甘肽转移酶和肌节蛋白跨组织的差异蛋白形式调节产生关于它们如何在人类健康和疾病中起作用和被调节的假设。
A functional understanding of the human body requires structure–function studies of proteins at scale. The chemical structure of proteins is controlled at the transcriptional, translational, and post-translational levels, creating a variety of products with modulated functions within the cell. The term “proteoform” encapsulates this complexity at the level of chemical composition. Comprehensive mapping of the proteoform landscape in human tissues necessitates analytical techniques with increased sensitivity and depth of coverage. Here, we took a top-down proteomics approach, combining data generated using capillary zone electrophoresis (CZE) and nanoflow reversed-phase liquid chromatography (RPLC) hyphenated to mass spectrometry to identify and characterize proteoforms from the human lungs, heart, spleen, small intestine, and kidneys. CZE and RPLC provided complementary post-translational modification and proteoform selectivity, thereby enhancing the overall proteome coverage when used in combination. Of the 11,466 proteoforms identified in this study, 7373 (64%) were not reported previously. Large differences in the protein and proteoform level were readily quantified, with initial inferences about proteoform biology operative in the analyzed organs. Differential proteoform regulation of defensins, glutathione transferases, and sarcomeric proteins across tissues generate hypotheses about how they function and are regulated in human health and disease.
登录
查看更多内容
影响因子：
4.4
作者：
LeDuc, Richard D.;Fellers, Ryan T.;Early, Bryan P.;Greer, Joseph B.;Thomas, Paul M.;Kelleher, Neil L.
通讯作者：
Kelleher, Neil L.
影响因子：
56.9
作者：
Melani, Rafael D.;Gerbasi, Vincent R.;Anderson, Lissa C.;Sikora, Jacek W.;Toby, Timothy K.;Hutton, Josiah E.;Butcher, David S.;Negrao, Fernanda;Seckler, Henrique S.;Srzentic, Kristina;Fornelli, Luca;Camarillo, Jeannie M.;LeDuc, Richard D.;Cesnik, Anthony J.;Lundberg, Emma;Greer, Joseph B.;Fellers, Ryan T.;Robey, Matthew T.;DeHart, Caroline J.;Forte, Eleonora;Hendrickson, Christopher L.;Abbatiello, Susan E.;Thomas, Paul M.;Kokaji, Andy, I;Levitsky, Josh;Kelleher, Neil L.
通讯作者：
Kelleher, Neil L.
影响因子：
48
作者：
Giesen, Charlotte;Wang, Hao A. O.;Bodenmiller, Bernd
通讯作者：
Bodenmiller, Bernd
影响因子：
13.6
作者：
Keren, Leeat;Bosse, Marc;Angelo, Michael
通讯作者：
Angelo, Michael
影响因子：
4.4
作者：
Fornelli, Luca;Durbin, Kenneth R.;Kelleher, Neil L.
通讯作者：
Kelleher, Neil L.