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Highly diversified expansions shaped the evolution of membrane bound proteins in metazoans
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.ORCID iD: 0000-0001-7112-0921
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 12387Article in journal (Refereed) Published
Abstract [en]

The dramatic increase in membrane proteome complexity is arguably one of the most pivotal evolutionary events that underpins the origin of multicellular animals. However, the origin of a significant number of membrane families involved in metazoan development has not been clarified. In this study, we have manually curated the membrane proteomes of 22 metazoan and 2 unicellular holozoan species. We identify 123,014 membrane proteins in these 24 eukaryotic species and classify 86% of the dataset. We determine 604 functional clusters that are present from the last holozoan common ancestor (LHCA) through many metazoan species. Intriguingly, we show that more than 70% of the metazoan membrane protein families have a premetazoan origin. The data show that enzymes are more highly represented in the LHCA and expand less than threefold throughout metazoan species; in contrast to receptors that are relatively few in the LHCA but expand nearly eight fold within metazoans. Expansions related to cell adhesion, communication, immune defence, and developmental processes are shown in conjunction with emerging biological systems, such as neuronal development, cytoskeleton organization, and the adaptive immune response. This study defines the possible LHCA membrane proteome and describes the fundamental functional clusters that underlie metazoan diversity and innovation.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2017. Vol. 7, article id 12387
National Category
Developmental Biology
Identifiers
URN: urn:nbn:se:uu:diva-337094DOI: 10.1038/s41598-017-11543-zISI: 000412000100002PubMedID: 28959054OAI: oai:DiVA.org:uu-337094DiVA, id: diva2:1171650
Funder
Swedish Research CouncilAvailable from: 2018-01-08 Created: 2018-01-08 Last updated: 2020-03-28Bibliographically approved
In thesis
1. Membrane-bound proteins: Characterization, evolution, and functional analysis
Open this publication in new window or tab >>Membrane-bound proteins: Characterization, evolution, and functional analysis
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Alpha-helical transmembrane proteins are important components of many essential cell processes including signal transduction, transport of molecules across membranes, protein and membrane trafficking, and structural and adhesion activities, amongst others. Their involvement in critical networks makes them the focus of interest in investigating disease pathways, as candidate drug targets, and in evolutionary analyses to identify homologous protein families and possible functional activities. Transmembrane (TM) proteins can be categorized into major groups based the same gross structure, i.e., the number of transmembrane helices, which are often correlated with specific functional activities, for example as receptors or transporters. The focus of this thesis was to analyze the evolution of the membrane proteome from the last holozoan common ancestor (LHCA) through metazoans to garner insight into the fundamental functional clusters that underlie metazoan diversity and innovation. Twenty-four eukaryotic proteomes were analyzed, with results showing more than 70% of metazoan transmembrane protein families have a pre-metazoan origin. In concert with that, we characterized the previously unstudied groups of human proteins with three, four, and five membrane-spanning regions (3TM, 4TM, and 5TM) and analyzed their functional activities, involvement in disease pathways, and unique characteristics. Combined, we manually curated and classified nearly 11% of the human transmembrane proteome with these three studies. The 3TM data set included 152 proteins, with nearly 45% that localize specifically to the endoplasmic reticulum (ER), and are involved in membrane biosynthesis and lipid biogenesis, proteins trafficking, catabolic processes, and signal transduction due to the large ionotropic glutamate receptor family. The 373 proteins identified in the 4TM data set are predominantly involved in transport activities, as well as cell communication and adhesion, and function as structural elements. The compact 5TM data set includes 58 proteins that engage in localization and transport activities, such as protein targeting, membrane trafficking, and vesicle transport. Notably, ~60% are identified as cancer prognostic markers that are associated with clinical outcomes of different tumour types. This thesis investigates the evolutionary origins of the human transmembrane proteome, characterizes formerly dark areas of the membrane proteome, and extends the fundamental knowledge of transmembrane proteins.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 45
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1660
Keywords
Transmembrane protein, alpha-helical membrane protein, evolution membrane proteins, 3TM, 4TM, 5TM, trispanin
National Category
Neurosciences
Research subject
Bioinformatics
Identifiers
urn:nbn:se:uu:diva-407778 (URN)978-91-513-0926-2 (ISBN)
Public defence
2020-05-25, Room A1:107, Uppsala Biomedicinska Centrum (BMC), Husargatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2020-05-04 Created: 2020-03-28 Last updated: 2020-05-15

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Attwood, Misty M.Krishnan, ArunkumarSchiöth, Helgi B.

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