LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3 [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 610.73 Nursing and services of allied health personnel
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2014
• Mô tả vật lý: Size: p. 26-32 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261309
• Chủ đề: 1. 59 basic biological sciences; 2. 60 applied life sciences; 3. Acyltransferase; 4. Biochemistry; 5. Enzyme mechanisms; 6. Et al; 7. Lrat; 8. Membranes; 9. Retinol; 10. Vitamin a; 11. X-ray crystallography

Tóm tắt

Cellular uptake of vitamin A, production of visual chromophore and triglyceride homeostasis in adipocytes depend on two representatives of the vertebrate N1pC/P60 protein family, lecithin:retinol acyltransferase (LRAT) and HRAS-like tumor suppressor 3 (HRASLS3). Both proteins function as lipid-metabolizing enzymes but differ in their substrate preferences and dominant catalytic activity. The mechanism of this catalytic diversity is not understood. In this paper, by using a gain-of-function approach, we identified a specific sequence responsible for the substrate specificity of N1pC/P60 proteins. A 2.2-� crystal structure of the HRASLS3-LRAT chimeric enzyme in a thioester catalytic intermediate state revealed a major structural rearrangement accompanied by three-dimensional domain swapping dimerization not observed in native HRASLS proteins. Structural changes affecting the active site environment contributed to slower hydrolysis of the catalytic intermediate, supporting efficient acyl transfer. Finally, these findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family.