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Unique two conjugation systems required for autophagy (237.1)
Author(s) -
Ohsumi Yoshinori
Publication year - 2014
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.28.1_supplement.237.1
Subject(s) - atg12 , atg8 , atg5 , autophagy , conjugate , lipid anchored protein , autophagosome , microbiology and biotechnology , chemistry , biology , biochemistry , apoptosis , mathematical analysis , mathematics
In autophagy two ubiqutination‐like conjugation systems play essential roles in the membrane formation of autophagosome. In yeast among 18 Atg proteins essential for autophagy 8 proteins are involved in these reactions. Atg12 forms a conjugate with Atg5 via E1 (Atg7) and E2 (Atg10) enzymes. Another UBL, Atg8 is activated by the same E1 and transferred to E2 (Atg3) and finally forms a conjugate with a phospholipid, phosphatidylethanolamine (PE). These systems have several unique features. Atg5 is the only target of Atg12, and Atg12‐Atg5 conjugate is constitutively formed, and dimerizes by binding to Atg16 dimer. Not only Atg7 is a common E1 enzyme for Atg12 and Atg8, but also two systems function closely. Atg12 system is required for Atg8‐PE formation. We showed that Atg12‐Atg5 conjugate has E3 like activity for Atg8 lipidation, enhancing Atg3 activity of the transfer reaction of Atg8 to PE. In collaboration with N. Noda (IMC) and F. Inagaki (Hokkaido Univ) we have solved crystal structures of most Atg proteins involved in the conjugation reactions. Present our knowledge on the roles of these conjugation systems in autophagy will be presented and discussed.