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Nonenzymatic and Enzymatic Functions of the Skp1 αGalactosyltransferase in Dictyostelium Oxygen‐Sensing
Author(s) -
Schafer Christopher M.,
Zhang Dongmei,
West Christopher M.
Publication year - 2012
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.26.1_supplement.607.7
Subject(s) - skp1 , dictyostelium , dictyostelium discoideum , biochemistry , glycosyltransferase , microbiology and biotechnology , allosteric regulation , enzyme , chemistry , biology , gene , ubiquitin , ubiquitin ligase
In the social amoeba Dictyostelium discoideum the SCF E3 adaptor protein Skp1 is modified by a prolyl hydroxylase and three glycosyltransferases. Aberrant expression of these enzyme proteins has been shown to affect development of Dictyostelium in response to environmental O 2 levels. The final enzyme in the pathway, AgtA (α3‐galactosyltransferase), modifies the core trisaccharide with 2 αGal residues. AgtA is unique being the only enzyme possessing a non‐catalytic domain. The C‐terminal domain contains 7 WD40‐repeats predicted to fold into a β‐propeller. in vitro activity studies comparing Skp1 glycoforms and free sugars implicate this domain in binding to Skp1 and allosteric modulation of the AgtA active site. Furthermore, biochemical and cell biological studies with single and double enzyme knockouts and overexpression strains suggest the WD40 domain may mediate a more complex role played by AgtA in the Skp1‐modification pathway via interference with other Skp1‐interacting proteins. From these data is emerging a model in which non‐enzymatic functions of AgtA serve to regulate the modification status and activity of Skp1 in a fashion unique among glycosyltransferases, with corresponding impact on O 2 ‐sensing in Dictyostelium and possibly other protists that share pathway genes. (Supported by NIH grants R01‐GM37539 & R01‐GM84383)