Velho Renata Voltolini, De Pace Raffaella, Tidow Henning, Braulke Thomas, Pohl Sandra
Section Biochemistry, Children's Hospital, University Medical Center Hamburg-Eppendorf, Germany.
Institute for Biochemistry and Molecular Biology, University of Hamburg, Germany.
FEBS Lett. 2016 Dec;590(23):4287-4295. doi: 10.1002/1873-3468.12456. Epub 2016 Oct 25.
The disease-associated hexameric N-acetylglucosamine (GlcNAc)-1-phosphotransferase complex (α β γ ) catalyzes the formation of mannose 6-phosphate residues on lysosomal enzymes required for efficient targeting to lysosomes. Using pull-down experiments and mutant subunits, we identified a potential loop-like region in the α-subunits comprising residues 535-588 and 645-698 involved in the binding to γ-subunits. The interaction is independent of the mannose 6-phosphate receptor homology domain but requires the N-terminal unstructured part of the γ-subunit consisting of residues 26-69. These studies provide new insights into structural requirements for the assembly of the GlcNAc-1-phosphotransferase complex, and the functions of distinct domains of the α- and γ-subunits.
与疾病相关的六聚体N-乙酰葡糖胺（GlcNAc）-1-磷酸转移酶复合物（αβγ）催化高效靶向溶酶体所需的溶酶体酶上甘露糖6-磷酸残基的形成。通过下拉实验和突变亚基，我们在α亚基中鉴定出一个潜在的环状区域，其包含参与与γ亚基结合的535-588位和645-698位残基。这种相互作用不依赖于甘露糖6-磷酸受体同源结构域，但需要由26-69位残基组成的γ亚基的N端无结构部分。这些研究为GlcNAc-1-磷酸转移酶复合物组装的结构要求以及α和γ亚基不同结构域的功能提供了新的见解。
