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Domain IV of Annexin A5 Is Critical for Binding Calcium and Guarantees Its Maximum Binding to the Phosphatidylserine Membrane
Background: Although domain IV of annexin A5 (anxA5) may be less effective in binding phosphatidylserine (PS), the four domains together may guarantee the maximum binding of anxA5 to the PS membrane. Additionally, previous research has shown that annexin mutants lacking one or more domain(s) have di...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6149819/ https://www.ncbi.nlm.nih.gov/pubmed/29257055 http://dx.doi.org/10.3390/molecules22122256 |
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author | Wang, Jie Liu, Jing Cao, Yulu Hu, Minjin Hua, Zichun |
author_facet | Wang, Jie Liu, Jing Cao, Yulu Hu, Minjin Hua, Zichun |
author_sort | Wang, Jie |
collection | PubMed |
description | Background: Although domain IV of annexin A5 (anxA5) may be less effective in binding phosphatidylserine (PS), the four domains together may guarantee the maximum binding of anxA5 to the PS membrane. Additionally, previous research has shown that annexin mutants lacking one or more domain(s) have different biological activities compared to the wild-type. The present research mainly aims to study the role of domain IV in the crucial PS-binding function of anxA5. Methods: The domain IV-truncated anxA5 protein was constructed and purified. Isothermal titration calorimetry, flow cytometry and activated partial thromboplastin time were adopted to examine the function of domain IV in anxA5-PS binding directly or indirectly. Results: The domain IV-truncated form of anxA5 is impaired in binding PS liposome and apoptotic cells, and anticoagulation activity. The mutant cannot bind calcium, but binds PS only in the presence of calcium. Conclusions: Truncation of domain IV of anxA5 destroys its calcium-binding ability and impairs its PS-binding activity. Truncation of domain IV may induce conformation change of anxA5 or reduce the hydrophobic interactions between protein and membrane, which may explain the decrease of PS-binding affinity of the mutant. |
format | Online Article Text |
id | pubmed-6149819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61498192018-11-13 Domain IV of Annexin A5 Is Critical for Binding Calcium and Guarantees Its Maximum Binding to the Phosphatidylserine Membrane Wang, Jie Liu, Jing Cao, Yulu Hu, Minjin Hua, Zichun Molecules Article Background: Although domain IV of annexin A5 (anxA5) may be less effective in binding phosphatidylserine (PS), the four domains together may guarantee the maximum binding of anxA5 to the PS membrane. Additionally, previous research has shown that annexin mutants lacking one or more domain(s) have different biological activities compared to the wild-type. The present research mainly aims to study the role of domain IV in the crucial PS-binding function of anxA5. Methods: The domain IV-truncated anxA5 protein was constructed and purified. Isothermal titration calorimetry, flow cytometry and activated partial thromboplastin time were adopted to examine the function of domain IV in anxA5-PS binding directly or indirectly. Results: The domain IV-truncated form of anxA5 is impaired in binding PS liposome and apoptotic cells, and anticoagulation activity. The mutant cannot bind calcium, but binds PS only in the presence of calcium. Conclusions: Truncation of domain IV of anxA5 destroys its calcium-binding ability and impairs its PS-binding activity. Truncation of domain IV may induce conformation change of anxA5 or reduce the hydrophobic interactions between protein and membrane, which may explain the decrease of PS-binding affinity of the mutant. MDPI 2017-12-19 /pmc/articles/PMC6149819/ /pubmed/29257055 http://dx.doi.org/10.3390/molecules22122256 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Jie Liu, Jing Cao, Yulu Hu, Minjin Hua, Zichun Domain IV of Annexin A5 Is Critical for Binding Calcium and Guarantees Its Maximum Binding to the Phosphatidylserine Membrane |
title | Domain IV of Annexin A5 Is Critical for Binding Calcium and Guarantees Its Maximum Binding to the Phosphatidylserine Membrane |
title_full | Domain IV of Annexin A5 Is Critical for Binding Calcium and Guarantees Its Maximum Binding to the Phosphatidylserine Membrane |
title_fullStr | Domain IV of Annexin A5 Is Critical for Binding Calcium and Guarantees Its Maximum Binding to the Phosphatidylserine Membrane |
title_full_unstemmed | Domain IV of Annexin A5 Is Critical for Binding Calcium and Guarantees Its Maximum Binding to the Phosphatidylserine Membrane |
title_short | Domain IV of Annexin A5 Is Critical for Binding Calcium and Guarantees Its Maximum Binding to the Phosphatidylserine Membrane |
title_sort | domain iv of annexin a5 is critical for binding calcium and guarantees its maximum binding to the phosphatidylserine membrane |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6149819/ https://www.ncbi.nlm.nih.gov/pubmed/29257055 http://dx.doi.org/10.3390/molecules22122256 |
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