Electrostatic interactions between single arginine and phospholipids modulate physiological properties of sarcoplasmic reticulum Ca2+-ATPase
Abstract Arg324 of sarcoplasmic reticulum Ca2+-ATPase forms electrostatic interactions with the phosphate moiety of phospholipids in most reaction states, and a hydrogen bond with Tyr122 in other states. Using site-directed mutagenesis, we explored the functional roles of Arg324 interactions, especi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-16091-9 |
| _version_ | 1828746848660094976 |
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| author | Kazuo Yamasaki Takashi Daiho Satoshi Yasuda Stefania Danko Jun-ichi Kawabe Hiroshi Suzuki |
| author_facet | Kazuo Yamasaki Takashi Daiho Satoshi Yasuda Stefania Danko Jun-ichi Kawabe Hiroshi Suzuki |
| author_sort | Kazuo Yamasaki |
| collection | DOAJ |
| description | Abstract Arg324 of sarcoplasmic reticulum Ca2+-ATPase forms electrostatic interactions with the phosphate moiety of phospholipids in most reaction states, and a hydrogen bond with Tyr122 in other states. Using site-directed mutagenesis, we explored the functional roles of Arg324 interactions, especially those with lipids, which at first glance might seem too weak to modulate the function of such a large membrane protein. The hydrogen bond forms transiently and facilitates Ca2+ binding from the cytoplasmic side. The contributions of the electrostatic interactions to the reaction steps were quantified using a rate vs activity coefficient plot. We found that the interaction between Arg324 and lipids decreases the affinity for luminal Ca2+. The transformation rate of the phosphoenzyme intermediate is facilitated by the electrostatic interactions, and the function of these interactions depends not only on the type but also on the composition of the phospholipids. The properties observed in microsomes could not be reproduced with any single phospholipid, but with a mixture of phospholipids that mimics the native membrane. These results suggest the importance of swapping of the lipid partners of different headgroups in the reaction step. This study shows that Arg324 plays a role in the reaction cycle via complex intra-protein and protein-lipid interactions. |
| first_indexed | 2024-04-14T04:32:13Z |
| format | Article |
| id | doaj.art-cde8cc0e189a45628f84d8db218ab550 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-14T04:32:13Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-cde8cc0e189a45628f84d8db218ab5502022-12-22T02:12:01ZengNature PortfolioScientific Reports2045-23222022-07-0112111210.1038/s41598-022-16091-9Electrostatic interactions between single arginine and phospholipids modulate physiological properties of sarcoplasmic reticulum Ca2+-ATPaseKazuo Yamasaki0Takashi Daiho1Satoshi Yasuda2Stefania Danko3Jun-ichi Kawabe4Hiroshi Suzuki5Department of Biochemistry, Asahikawa Medical UniversityDepartment of Biochemistry, Asahikawa Medical UniversityDepartment of Biochemistry, Asahikawa Medical UniversityDepartment of Biochemistry, Asahikawa Medical UniversityDepartment of Biochemistry, Asahikawa Medical UniversityDepartment of Biochemistry, Asahikawa Medical UniversityAbstract Arg324 of sarcoplasmic reticulum Ca2+-ATPase forms electrostatic interactions with the phosphate moiety of phospholipids in most reaction states, and a hydrogen bond with Tyr122 in other states. Using site-directed mutagenesis, we explored the functional roles of Arg324 interactions, especially those with lipids, which at first glance might seem too weak to modulate the function of such a large membrane protein. The hydrogen bond forms transiently and facilitates Ca2+ binding from the cytoplasmic side. The contributions of the electrostatic interactions to the reaction steps were quantified using a rate vs activity coefficient plot. We found that the interaction between Arg324 and lipids decreases the affinity for luminal Ca2+. The transformation rate of the phosphoenzyme intermediate is facilitated by the electrostatic interactions, and the function of these interactions depends not only on the type but also on the composition of the phospholipids. The properties observed in microsomes could not be reproduced with any single phospholipid, but with a mixture of phospholipids that mimics the native membrane. These results suggest the importance of swapping of the lipid partners of different headgroups in the reaction step. This study shows that Arg324 plays a role in the reaction cycle via complex intra-protein and protein-lipid interactions.https://doi.org/10.1038/s41598-022-16091-9 |
| spellingShingle | Kazuo Yamasaki Takashi Daiho Satoshi Yasuda Stefania Danko Jun-ichi Kawabe Hiroshi Suzuki Electrostatic interactions between single arginine and phospholipids modulate physiological properties of sarcoplasmic reticulum Ca2+-ATPase Scientific Reports |
| title | Electrostatic interactions between single arginine and phospholipids modulate physiological properties of sarcoplasmic reticulum Ca2+-ATPase |
| title_full | Electrostatic interactions between single arginine and phospholipids modulate physiological properties of sarcoplasmic reticulum Ca2+-ATPase |
| title_fullStr | Electrostatic interactions between single arginine and phospholipids modulate physiological properties of sarcoplasmic reticulum Ca2+-ATPase |
| title_full_unstemmed | Electrostatic interactions between single arginine and phospholipids modulate physiological properties of sarcoplasmic reticulum Ca2+-ATPase |
| title_short | Electrostatic interactions between single arginine and phospholipids modulate physiological properties of sarcoplasmic reticulum Ca2+-ATPase |
| title_sort | electrostatic interactions between single arginine and phospholipids modulate physiological properties of sarcoplasmic reticulum ca2 atpase |
| url | https://doi.org/10.1038/s41598-022-16091-9 |
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