Integrin evolution : from prokaryotes to the diversification within chordates
Chouhan, Bhanupratap Singh (2016-10-14)
Chouhan, Bhanupratap Singh
Åbo Akademi - Åbo Akademi University
14.10.2016
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
Julkaisun pysyvä osoite on
https://urn.fi/URN:ISBN:978-952-12-3449-1
https://urn.fi/URN:ISBN:978-952-12-3449-1
Tiivistelmä
Integrins are a family of large multi-domain cell surface receptors responsible for bidirectional signaling in response to cell-cell, cell-extracellular matrix interactions as well as intracellular interactions. Intrgrins are implicated in a wide variety of functions such as inflammatory responses, adoptive antigen-specific immunity, tissue remodelling and cell adhesion, proliferation and differentiation. Furthermore, integrins are also known to be associated with a wide variety of diseases and health issues, such as tumour metastasis, immune dysfunction, inflammation, viral infections and osteoporosis – to name a few – making them one of the most complex cell adhesion molecules. Integrin are heterodimers which are composed of an α and a β subunit and humans are known to express 18 α subunits and 8 β subunits which associate non-covalently to form 24 α/β heterodimers out of 144 possible combinations. Orthologues of mammalian integrins are observed throughout vertebrates including the bony fish (osteichthyes), however integrins extracted from early chordates like the tunicates Ciona intestinalis or Halocynthia roretzi are not direct mammalian orthlogues. Even though integrins are observed throughout metazoans, studies have reported that integrins and their signaling machinery are located in unicellular eukaryotes. In addition, the 3D folds of the constituent domains from the integrin α and β subunits have also been detected in bacteria.
The major aims of the research work described in this thesis were to answer the following questions: i) When did the constituent domains from the integrin α and β subunits originate? ii) When did the α I-domains get integrated into the integrin heterodimer and when did the collagen-binding integrin α Idomains originate in the vertebrates? iii) When did the mammalian-type integrin orthologues originate in vertebrates?
In order to address these questions, we analysed the available sequences, genomic data as well as structural data, all of which are discussed in detail in the three studies comprising this thesis. During the course of this thesis: i) We have addressed the origin of pivotal integrin constituent domain like the N-terminal 7-bladed β-propeller domain from the α-subunit by investigating the extent of similarities between the sequences and structures of different integrin domains and similar gene products and protein sequences from bacteria. ii) We have identified characteristic structural features or motifs like the αC helix in order to understand the evolutionary process of collagen-binding integrin α I-domain in vertebrates. iii) Recent advancements in the genome assembly process of organisms like the sea lamprey (agnathostome) and the elephant shark (chondrichthyes) has helped us in understanding the origin and evolution of mammalian-type integrin orthologues. In conclusion, the studies presented in this thesis present novel insights into the evolutionary patterns of the integrins.
The major aims of the research work described in this thesis were to answer the following questions: i) When did the constituent domains from the integrin α and β subunits originate? ii) When did the α I-domains get integrated into the integrin heterodimer and when did the collagen-binding integrin α Idomains originate in the vertebrates? iii) When did the mammalian-type integrin orthologues originate in vertebrates?
In order to address these questions, we analysed the available sequences, genomic data as well as structural data, all of which are discussed in detail in the three studies comprising this thesis. During the course of this thesis: i) We have addressed the origin of pivotal integrin constituent domain like the N-terminal 7-bladed β-propeller domain from the α-subunit by investigating the extent of similarities between the sequences and structures of different integrin domains and similar gene products and protein sequences from bacteria. ii) We have identified characteristic structural features or motifs like the αC helix in order to understand the evolutionary process of collagen-binding integrin α I-domain in vertebrates. iii) Recent advancements in the genome assembly process of organisms like the sea lamprey (agnathostome) and the elephant shark (chondrichthyes) has helped us in understanding the origin and evolution of mammalian-type integrin orthologues. In conclusion, the studies presented in this thesis present novel insights into the evolutionary patterns of the integrins.