5yip
Crystal Structure of AnkG LIR/GABARAPL1 complex
Structural highlights
Function[GBRL1_MOUSE] Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (By similarity). [ANK3_RAT] Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments. In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (By similarity).[UniProtKB:G5E8K5] Publication Abstract from PubMedThe mammalian Atg8 family proteins are central drivers of autophagy and contain six members, classified into the LC3 and GABARAP subfamilies. Due to their high sequence similarity and consequent functional overlaps, it is difficult to delineate specific functions of Atg8 proteins in autophagy. Here we discover a super-strong GABARAP-selective inhibitory peptide harbored in 270/480 kDa ankyrin-G and a super-potent pan-Atg8 inhibitory peptide from 440 kDa ankyrin-B. Structural studies elucidate the mechanism governing the Atg8 binding potency and selectivity of the peptides, reveal a general Atg8-binding sequence motif, and allow development of a more GABARAP-selective inhibitory peptide. These peptides effectively blocked autophagy when expressed in cultured cells. Expression of these ankyrin-derived peptides in Caenorhabditis elegans also inhibited autophagy, causing accumulation of the p62 homolog SQST-1, delayed development and shortened life span. Thus, these genetically encodable autophagy inhibitory peptides can be used to occlude autophagy spatiotemporally in living animals. Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins.,Li J, Zhu R, Chen K, Zheng H, Zhao H, Yuan C, Zhang H, Wang C, Zhang M Nat Chem Biol. 2018 Jun 4. pii: 10.1038/s41589-018-0082-8. doi:, 10.1038/s41589-018-0082-8. PMID:29867141[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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