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Structural analysis of GPS autoproteolysis of LNB‐TM7 receptors‐Characterization of the interaction between the extracellular α‐subunit and the 7TM β‐subunit
Author(s) -
Huang YiShun,
Lin HsiHsien
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.879.5
Subject(s) - protein subunit , extracellular , receptor , microbiology and biotechnology , chemistry , transmembrane domain , cell membrane , cell , biochemistry , biology , gene
The novel class B2 GPCRs (LNB‐TM7) have been found to undergo post‐translational autoproteolysis at the G protein‐coupled receptor proteolytic site (GPS) in the ER. Therefore, the GPS autoproteolysis of LNB‐TM7 receptors produces constitutively two subunits, a large extracellular domain (α‐subunit) resembling cell‐adhesion protein and a TM7 domain (β‐subunit) that is a typical TM7 moiety of GPCR. Intriguingly, the cleaved α‐subunit was shown to remain firmly on the cell membrane. It has long been believed that the α‐subunit interacts non‐covalently with the β‐subunit to form a heterodimeric structure on the cell membrane. However, based on our data and others, it is shown that the α‐subunit and β‐subunit do not normally interact on the cell membrane and behave rather as two separate proteins. First, we find that PFO can dissociate the α‐subunit of cellular form but not soluble form. Second, we find that the α‐subunit does not associate with soluble CD4 fragment secreted into conditioned medium and does not associate with the CD4 fragment moved to the lipid raft region. Third, we find that the α‐subunit is retained in the ER by non‐covalent interaction with the β‐subunit. Hence, it is hoped that the results from our investigation will provide some important clues to decipher the cellular functions and human diseases associated with the LNB‐TM7 receptors. NSC96‐2320‐B‐182‐005