Insights into autophagosome maturation revealed by the structures of ATG5 with its interacting partners

Jun Hoe Kim, Seung Beom Hong, Jae Keun Lee, Sisu Han, Kyung Hye Roh, Kyung Eun Lee, Yoon Ki Kim, Eui Ju Choi, Hyun Kyu Song

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Autophagy is a bulky catabolic process that responds to nutrient homeostasis and extracellular stress signals and is a conserved mechanism in all eukaryotes. When autophagy is induced, cellular components are sequestered within an autophagosome and finally degraded by subsequent fusion with a lysosome. During this process, the ATG12-ATG5 conjugate requires 2 different binding partners, ATG16L1 for autophagosome elongation and TECPR1 for lysosomal fusion. In our current study, we describe the crystal structures of human ATG5 in complex with an N-terminal domain of ATG16L1 as well as an internal AIR domain of TECPR1. Both binding partners exhibit a similar a-helical structure containing a conserved binding motif termed AFIM. Furthermore, we characterize the critical role of the C-terminal unstructured region of the AIR domain of TECPR1. These fi ndings are further confirmed by biochemical and cell biological analyses. These results provide new insights into the molecular details of the autophagosome maturation process, from its elongation to its fusion with a lysosome.

Original languageEnglish
Pages (from-to)75-87
Number of pages13
JournalAutophagy
Volume11
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1

Fingerprint

Autophagy
Lysosomes
Eukaryota
Homeostasis
Food
Autophagosomes

Keywords

  • ATG12
  • ATG16
  • ATG5
  • Crystal structure
  • Lysosome fusion
  • TECPR1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Insights into autophagosome maturation revealed by the structures of ATG5 with its interacting partners. / Kim, Jun Hoe; Hong, Seung Beom; Lee, Jae Keun; Han, Sisu; Roh, Kyung Hye; Lee, Kyung Eun; Kim, Yoon Ki; Choi, Eui Ju; Song, Hyun Kyu.

In: Autophagy, Vol. 11, No. 1, 01.01.2015, p. 75-87.

Research output: Contribution to journalArticle

Kim, Jun Hoe ; Hong, Seung Beom ; Lee, Jae Keun ; Han, Sisu ; Roh, Kyung Hye ; Lee, Kyung Eun ; Kim, Yoon Ki ; Choi, Eui Ju ; Song, Hyun Kyu. / Insights into autophagosome maturation revealed by the structures of ATG5 with its interacting partners. In: Autophagy. 2015 ; Vol. 11, No. 1. pp. 75-87.
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