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Human organic anion transporting polypeptide 1B3 (OATP1B3) is more heavily N-glycosylated than OATP1B1 in extracellular loops 2 and 5.
Liang, Ting; Liu, Han; Li, Lanjing; Huan, Ru; Gui, Chunshan.
Afiliación
  • Liang T; College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.
  • Liu H; College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.
  • Li L; College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.
  • Huan R; College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.
  • Gui C; College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China. Electronic address: guichunshan@suda.edu.cn.
Int J Biol Macromol ; 278(Pt 2): 134748, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39147348
ABSTRACT
Human organic anion transporting polypeptide 1B3 (OATP1B3) and 1B1 are two liver-specific and highly homologous uptake transporters, whose structures consist of 12 transmembrane domains. The present study showed that OATP1B3 is more heavily N-glycosylated than OATP1B1 in extracellular loop 2 (EL2) and EL5. OATP1B3 has six N-glycosylation sites, namely N134, N145, N151, N445, N503, and N516, which is twice of that of OATP1B1. Single removal of individual N-glycans seems to have minimal influence on the surface expression and function of OATP1B3. However, simultaneous removal of all N-glycans will lead to OATP1B3's large retention in the endoplasmic reticulum and cellular degradation and thus significantly disrupts its surface expression. While N-glycosylation plays a crucial role in the surface expression of OATP1B3, it also has some effect on the transport function of OATP1B3 per se, which is not due to a decrease of substrate binding affinity but due to a reduced transporter's turnover number. Taken together, N-glycosylation is essential for normal surface expression and function of OATP1B3. Its disruption by some liver diseases such as NASH might alter the pharmacokinetic/pharmacodynamic properties of OATP1B3's substrate drugs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transportador 1 de Anión Orgánico Específico del Hígado / Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos Límite: Humans Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transportador 1 de Anión Orgánico Específico del Hígado / Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos Límite: Humans Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos