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Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly
Assembly of protein complexes is facilitated by assembly chaperones. Alpha and gamma adaptin-binding protein (AAGAB) is a chaperone governing the assembly of the heterotetrameric adaptor complexes 1 and 2 (AP1 and AP2) involved in clathrin-mediated membrane trafficking. Here, we found that before AP...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926252/ https://www.ncbi.nlm.nih.gov/pubmed/36598941 http://dx.doi.org/10.1073/pnas.2205199120 |
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author | Tian, Yuan Datta, Ishara Yang, Rui Wan, Chun Wang, Bing Crisman, Lauren He, Huan Brautigam, Chad A. Li, Suzhao Shen, Jingshi Yin, Qian |
author_facet | Tian, Yuan Datta, Ishara Yang, Rui Wan, Chun Wang, Bing Crisman, Lauren He, Huan Brautigam, Chad A. Li, Suzhao Shen, Jingshi Yin, Qian |
author_sort | Tian, Yuan |
collection | PubMed |
description | Assembly of protein complexes is facilitated by assembly chaperones. Alpha and gamma adaptin-binding protein (AAGAB) is a chaperone governing the assembly of the heterotetrameric adaptor complexes 1 and 2 (AP1 and AP2) involved in clathrin-mediated membrane trafficking. Here, we found that before AP1/2 binding, AAGAB exists as a homodimer. AAGAB dimerization is mediated by its C-terminal domain (CTD), which is critical for AAGAB stability and is missing in mutant proteins found in patients with the skin disease punctate palmoplantar keratoderma type 1 (PPKP1). We solved the crystal structure of the dimerization-mediating CTD, revealing an antiparallel dimer of bent helices. Interestingly, AAGAB uses the same CTD to recognize and stabilize the γ subunit in the AP1 complex and the α subunit in the AP2 complex, forming binary complexes containing only one copy of AAGAB. These findings demonstrate a dual role of CTD in stabilizing resting AAGAB and binding to substrates, providing a molecular explanation for disease-causing AAGAB mutations. The oligomerization state transition mechanism may also underlie the functions of other assembly chaperones. |
format | Online Article Text |
id | pubmed-9926252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-99262522023-07-04 Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly Tian, Yuan Datta, Ishara Yang, Rui Wan, Chun Wang, Bing Crisman, Lauren He, Huan Brautigam, Chad A. Li, Suzhao Shen, Jingshi Yin, Qian Proc Natl Acad Sci U S A Biological Sciences Assembly of protein complexes is facilitated by assembly chaperones. Alpha and gamma adaptin-binding protein (AAGAB) is a chaperone governing the assembly of the heterotetrameric adaptor complexes 1 and 2 (AP1 and AP2) involved in clathrin-mediated membrane trafficking. Here, we found that before AP1/2 binding, AAGAB exists as a homodimer. AAGAB dimerization is mediated by its C-terminal domain (CTD), which is critical for AAGAB stability and is missing in mutant proteins found in patients with the skin disease punctate palmoplantar keratoderma type 1 (PPKP1). We solved the crystal structure of the dimerization-mediating CTD, revealing an antiparallel dimer of bent helices. Interestingly, AAGAB uses the same CTD to recognize and stabilize the γ subunit in the AP1 complex and the α subunit in the AP2 complex, forming binary complexes containing only one copy of AAGAB. These findings demonstrate a dual role of CTD in stabilizing resting AAGAB and binding to substrates, providing a molecular explanation for disease-causing AAGAB mutations. The oligomerization state transition mechanism may also underlie the functions of other assembly chaperones. National Academy of Sciences 2023-01-04 2023-01-10 /pmc/articles/PMC9926252/ /pubmed/36598941 http://dx.doi.org/10.1073/pnas.2205199120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Tian, Yuan Datta, Ishara Yang, Rui Wan, Chun Wang, Bing Crisman, Lauren He, Huan Brautigam, Chad A. Li, Suzhao Shen, Jingshi Yin, Qian Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly |
title | Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly |
title_full | Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly |
title_fullStr | Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly |
title_full_unstemmed | Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly |
title_short | Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly |
title_sort | oligomer-to-monomer transition underlies the chaperone function of aagab in ap1/ap2 assembly |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926252/ https://www.ncbi.nlm.nih.gov/pubmed/36598941 http://dx.doi.org/10.1073/pnas.2205199120 |
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