3wan
From Proteopedia
Crystal structure of Atg13 LIR-fused human LC3A_2-121
Structural highlights
Function[ATG13_HUMAN] Autophagy factor required for autophagosome formation and mitophagy. Target of the TOR kinase signaling pathway that regulates autophagy through the control of the phosphorylation status of ATG13 and ULK1, and the regulation of the ATG13-ULK1-RB1CC1 complex. Through its regulation of ULK1 activity, plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedAutophagy is a bulk degradation pathway that removes cytosolic materials to maintain cellular homeostasis. The autophagy-related gene 13 (Atg13) and microtubule associate protein 1 light chain 3 (LC3) proteins are required for autophagosome formation. We demonstrate that each of the human LC3 isoforms (LC3A, LC3B, and LC3C) interacts with Atg13 via the LC3 interacting region (LIR) of Atg13. Using X-ray crystallography, we solved the macromolecular structures of LC3A and LC3C, along with the complex structures of the LC3 isoforms with the Atg13 LIR. Together, our structural and binding analyses reveal that the side-chain of Lys49 of LC3 acts as a gatekeeper to regulate binding of the LIR. We verified this observation by mutation of Lys49 in LC3A, which significantly reduces LC3A positive puncta formation in cultured cells. Our results suggest that specific affinity of the LC3 isoforms to the Atg13 LIR is required for proper autophagosome formation. Structural Basis of the Autophagy-Related LC3/Atg13 LIR Complex: Recognition and Interaction Mechanism.,Suzuki H, Tabata K, Morita E, Kawasaki M, Kato R, Dobson RC, Yoshimori T, Wakatsuki S Structure. 2013 Nov 25. pii: S0969-2126(13)00401-2. doi:, 10.1016/j.str.2013.09.023. PMID:24290141[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Dobson, R C.J | Kato, R | Kawasaki, M | Morita, E | Suzuki, H | Tabata, K | Wakatsuki, S | Yoshimori, T | Autophagy | Protein binding | Ubiquitin-like fold
