Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles]
Fang, Z., Huang, J., Chen, J., Xu, S., Xiang, Z., Hong, M.
The American Society for Pharmacology and Experimental Therapeutics (ASPET)
Published 2018
The American Society for Pharmacology and Experimental Therapeutics (ASPET)
Published 2018
| Publication Date: |
2018-06-27
|
|---|---|
| Publisher: |
The American Society for Pharmacology and Experimental Therapeutics (ASPET)
|
| Print ISSN: |
0026-895X
|
| Electronic ISSN: |
1521-0111
|
| Topics: |
Chemistry and Pharmacology
Medicine
|
| Published by: |
| _version_ | 1836398987071979520 |
|---|---|
| autor | Fang, Z., Huang, J., Chen, J., Xu, S., Xiang, Z., Hong, M. |
| beschreibung | Organic anion transporting polypeptides (OATPs, gene symbol SLCO ) are important membrane transporter proteins that mediate the uptake of wide ranges of endogenous and exogenous compounds. OATP2B1 has been found in multiple organs and tissues, including the liver, small intestine, kidney, brain, placenta, heart, skin, as well as skeletal muscle, and is proposed to be involved in the uptake of orally administered drugs. Quite a few reports have demonstrated that transmembrane domains (TMs) are crucial for proper functions of OATP family members. Comparative modeling proposed that TM1, along with TM2, 4, and 5 of the N-terminal half of OATP2B1, may be localized within the substrate interaction pocket and are important for uptake function of the transporter. Alanine scanning of the putative transmembrane domain 1 of OATP2B1 revealed that substitution of L58 with alanine dramatically altered the K m value, and mutation of V52, H55, Q59, and L69 resulted in significantly reduced substrate turnover number, whereas A61V, Q62A, and S66A exhibited significant change in both K m and V max values. In addition, phenylalanine at position 51 seems to play an important role in maintaining proper folding of OATP2B1 because alanine replacement of F51 caused accelerated degradation of the transporter protein. Although proteasome and lysosome inhibitors could partially recover protein level, the mutant transporter remained nonfunctional. Taken together, the identification of nine essential amino acid residues within TM1 of OATP2B1 suggested that the transmembrane domain is important for maintaining proper function of the transporter. |
| citation_standardnr | 6292961 |
| datenlieferant | ipn_articles |
| feed_id | 1938 |
| feed_publisher | The American Society for Pharmacology and Experimental Therapeutics (ASPET) |
| feed_publisher_url | http://www.aspet.org/ |
| insertion_date | 2018-06-27 |
| journaleissn | 1521-0111 |
| journalissn | 0026-895X |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Society for Pharmacology and Experimental Therapeutics (ASPET) |
| quelle | Molecular Pharmacology |
| relation | http://molpharm.aspetjournals.org/cgi/content/short/94/2/842?rss=1 |
| search_space | articles |
| shingle_author_1 | Fang, Z., Huang, J., Chen, J., Xu, S., Xiang, Z., Hong, M. |
| shingle_author_2 | Fang, Z., Huang, J., Chen, J., Xu, S., Xiang, Z., Hong, M. |
| shingle_author_3 | Fang, Z., Huang, J., Chen, J., Xu, S., Xiang, Z., Hong, M. |
| shingle_author_4 | Fang, Z., Huang, J., Chen, J., Xu, S., Xiang, Z., Hong, M. |
| shingle_catch_all_1 | Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles] Organic anion transporting polypeptides (OATPs, gene symbol SLCO ) are important membrane transporter proteins that mediate the uptake of wide ranges of endogenous and exogenous compounds. OATP2B1 has been found in multiple organs and tissues, including the liver, small intestine, kidney, brain, placenta, heart, skin, as well as skeletal muscle, and is proposed to be involved in the uptake of orally administered drugs. Quite a few reports have demonstrated that transmembrane domains (TMs) are crucial for proper functions of OATP family members. Comparative modeling proposed that TM1, along with TM2, 4, and 5 of the N-terminal half of OATP2B1, may be localized within the substrate interaction pocket and are important for uptake function of the transporter. Alanine scanning of the putative transmembrane domain 1 of OATP2B1 revealed that substitution of L58 with alanine dramatically altered the K m value, and mutation of V52, H55, Q59, and L69 resulted in significantly reduced substrate turnover number, whereas A61V, Q62A, and S66A exhibited significant change in both K m and V max values. In addition, phenylalanine at position 51 seems to play an important role in maintaining proper folding of OATP2B1 because alanine replacement of F51 caused accelerated degradation of the transporter protein. Although proteasome and lysosome inhibitors could partially recover protein level, the mutant transporter remained nonfunctional. Taken together, the identification of nine essential amino acid residues within TM1 of OATP2B1 suggested that the transmembrane domain is important for maintaining proper function of the transporter. Fang, Z., Huang, J., Chen, J., Xu, S., Xiang, Z., Hong, M. The American Society for Pharmacology and Experimental Therapeutics (ASPET) 0026-895X 0026895X 1521-0111 15210111 |
| shingle_catch_all_2 | Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles] Organic anion transporting polypeptides (OATPs, gene symbol SLCO ) are important membrane transporter proteins that mediate the uptake of wide ranges of endogenous and exogenous compounds. OATP2B1 has been found in multiple organs and tissues, including the liver, small intestine, kidney, brain, placenta, heart, skin, as well as skeletal muscle, and is proposed to be involved in the uptake of orally administered drugs. Quite a few reports have demonstrated that transmembrane domains (TMs) are crucial for proper functions of OATP family members. Comparative modeling proposed that TM1, along with TM2, 4, and 5 of the N-terminal half of OATP2B1, may be localized within the substrate interaction pocket and are important for uptake function of the transporter. Alanine scanning of the putative transmembrane domain 1 of OATP2B1 revealed that substitution of L58 with alanine dramatically altered the K m value, and mutation of V52, H55, Q59, and L69 resulted in significantly reduced substrate turnover number, whereas A61V, Q62A, and S66A exhibited significant change in both K m and V max values. In addition, phenylalanine at position 51 seems to play an important role in maintaining proper folding of OATP2B1 because alanine replacement of F51 caused accelerated degradation of the transporter protein. Although proteasome and lysosome inhibitors could partially recover protein level, the mutant transporter remained nonfunctional. Taken together, the identification of nine essential amino acid residues within TM1 of OATP2B1 suggested that the transmembrane domain is important for maintaining proper function of the transporter. Fang, Z., Huang, J., Chen, J., Xu, S., Xiang, Z., Hong, M. The American Society for Pharmacology and Experimental Therapeutics (ASPET) 0026-895X 0026895X 1521-0111 15210111 |
| shingle_catch_all_3 | Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles] Organic anion transporting polypeptides (OATPs, gene symbol SLCO ) are important membrane transporter proteins that mediate the uptake of wide ranges of endogenous and exogenous compounds. OATP2B1 has been found in multiple organs and tissues, including the liver, small intestine, kidney, brain, placenta, heart, skin, as well as skeletal muscle, and is proposed to be involved in the uptake of orally administered drugs. Quite a few reports have demonstrated that transmembrane domains (TMs) are crucial for proper functions of OATP family members. Comparative modeling proposed that TM1, along with TM2, 4, and 5 of the N-terminal half of OATP2B1, may be localized within the substrate interaction pocket and are important for uptake function of the transporter. Alanine scanning of the putative transmembrane domain 1 of OATP2B1 revealed that substitution of L58 with alanine dramatically altered the K m value, and mutation of V52, H55, Q59, and L69 resulted in significantly reduced substrate turnover number, whereas A61V, Q62A, and S66A exhibited significant change in both K m and V max values. In addition, phenylalanine at position 51 seems to play an important role in maintaining proper folding of OATP2B1 because alanine replacement of F51 caused accelerated degradation of the transporter protein. Although proteasome and lysosome inhibitors could partially recover protein level, the mutant transporter remained nonfunctional. Taken together, the identification of nine essential amino acid residues within TM1 of OATP2B1 suggested that the transmembrane domain is important for maintaining proper function of the transporter. Fang, Z., Huang, J., Chen, J., Xu, S., Xiang, Z., Hong, M. The American Society for Pharmacology and Experimental Therapeutics (ASPET) 0026-895X 0026895X 1521-0111 15210111 |
| shingle_catch_all_4 | Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles] Organic anion transporting polypeptides (OATPs, gene symbol SLCO ) are important membrane transporter proteins that mediate the uptake of wide ranges of endogenous and exogenous compounds. OATP2B1 has been found in multiple organs and tissues, including the liver, small intestine, kidney, brain, placenta, heart, skin, as well as skeletal muscle, and is proposed to be involved in the uptake of orally administered drugs. Quite a few reports have demonstrated that transmembrane domains (TMs) are crucial for proper functions of OATP family members. Comparative modeling proposed that TM1, along with TM2, 4, and 5 of the N-terminal half of OATP2B1, may be localized within the substrate interaction pocket and are important for uptake function of the transporter. Alanine scanning of the putative transmembrane domain 1 of OATP2B1 revealed that substitution of L58 with alanine dramatically altered the K m value, and mutation of V52, H55, Q59, and L69 resulted in significantly reduced substrate turnover number, whereas A61V, Q62A, and S66A exhibited significant change in both K m and V max values. In addition, phenylalanine at position 51 seems to play an important role in maintaining proper folding of OATP2B1 because alanine replacement of F51 caused accelerated degradation of the transporter protein. Although proteasome and lysosome inhibitors could partially recover protein level, the mutant transporter remained nonfunctional. Taken together, the identification of nine essential amino acid residues within TM1 of OATP2B1 suggested that the transmembrane domain is important for maintaining proper function of the transporter. Fang, Z., Huang, J., Chen, J., Xu, S., Xiang, Z., Hong, M. The American Society for Pharmacology and Experimental Therapeutics (ASPET) 0026-895X 0026895X 1521-0111 15210111 |
| shingle_title_1 | Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles] |
| shingle_title_2 | Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles] |
| shingle_title_3 | Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles] |
| shingle_title_4 | Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles] |
| timestamp | 2025-06-30T23:35:48.412Z |
| titel | Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles] |
| titel_suche | Transmembrane Domain 1 of Human Organic Anion Transporting Polypeptide 2B1 Is Essential for Transporter Function and Stability [Articles] |
| topic | V WW-YZ |
| uid | ipn_articles_6292961 |