Structure of the human PKD1-PKD2 complex
Su, Q., Hu, F., Ge, X., Lei, J., Yu, S., Wang, T., Zhou, Q., Mei, C., Shi, Y.
American Association for the Advancement of Science (AAAS)
Published 2018
American Association for the Advancement of Science (AAAS)
Published 2018
| Publication Date: |
2018-09-07
|
|---|---|
| Publisher: |
American Association for the Advancement of Science (AAAS)
|
| Print ISSN: |
0036-8075
|
| Electronic ISSN: |
1095-9203
|
| Topics: |
Biology
Chemistry and Pharmacology
Geosciences
Computer Science
Medicine
Natural Sciences in General
Physics
|
| Keywords: |
Biochemistry, Online Only
|
| Published by: |
| _version_ | 1836399045590908928 |
|---|---|
| autor | Su, Q., Hu, F., Ge, X., Lei, J., Yu, S., Wang, T., Zhou, Q., Mei, C., Shi, Y. |
| beschreibung | Mutations in two genes, PKD1 and PKD2 , account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo–electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five–transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins. |
| citation_standardnr | 6329535 |
| datenlieferant | ipn_articles |
| feed_id | 25 |
| feed_publisher | American Association for the Advancement of Science (AAAS) |
| feed_publisher_url | http://www.aaas.org/ |
| insertion_date | 2018-09-07 |
| journaleissn | 1095-9203 |
| journalissn | 0036-8075 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | American Association for the Advancement of Science (AAAS) |
| quelle | Science |
| relation | http://science.sciencemag.org/cgi/content/short/361/6406/eaat9819?rss=1 |
| schlagwort | Biochemistry, Online Only |
| search_space | articles |
| shingle_author_1 | Su, Q., Hu, F., Ge, X., Lei, J., Yu, S., Wang, T., Zhou, Q., Mei, C., Shi, Y. |
| shingle_author_2 | Su, Q., Hu, F., Ge, X., Lei, J., Yu, S., Wang, T., Zhou, Q., Mei, C., Shi, Y. |
| shingle_author_3 | Su, Q., Hu, F., Ge, X., Lei, J., Yu, S., Wang, T., Zhou, Q., Mei, C., Shi, Y. |
| shingle_author_4 | Su, Q., Hu, F., Ge, X., Lei, J., Yu, S., Wang, T., Zhou, Q., Mei, C., Shi, Y. |
| shingle_catch_all_1 | Structure of the human PKD1-PKD2 complex Biochemistry, Online Only Mutations in two genes, PKD1 and PKD2 , account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo–electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five–transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins. Su, Q., Hu, F., Ge, X., Lei, J., Yu, S., Wang, T., Zhou, Q., Mei, C., Shi, Y. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_2 | Structure of the human PKD1-PKD2 complex Biochemistry, Online Only Mutations in two genes, PKD1 and PKD2 , account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo–electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five–transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins. Su, Q., Hu, F., Ge, X., Lei, J., Yu, S., Wang, T., Zhou, Q., Mei, C., Shi, Y. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_3 | Structure of the human PKD1-PKD2 complex Biochemistry, Online Only Mutations in two genes, PKD1 and PKD2 , account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo–electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five–transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins. Su, Q., Hu, F., Ge, X., Lei, J., Yu, S., Wang, T., Zhou, Q., Mei, C., Shi, Y. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_4 | Structure of the human PKD1-PKD2 complex Biochemistry, Online Only Mutations in two genes, PKD1 and PKD2 , account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo–electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five–transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins. Su, Q., Hu, F., Ge, X., Lei, J., Yu, S., Wang, T., Zhou, Q., Mei, C., Shi, Y. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_title_1 | Structure of the human PKD1-PKD2 complex |
| shingle_title_2 | Structure of the human PKD1-PKD2 complex |
| shingle_title_3 | Structure of the human PKD1-PKD2 complex |
| shingle_title_4 | Structure of the human PKD1-PKD2 complex |
| timestamp | 2025-06-30T23:36:43.370Z |
| titel | Structure of the human PKD1-PKD2 complex |
| titel_suche | Structure of the human PKD1-PKD2 complex |
| topic | W V TE-TZ SQ-SU WW-YZ TA-TD U |
| uid | ipn_articles_6329535 |