Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange
Actin assembly is important for cell motility. The ability of actin subunits to join or leave filaments via the barbed end is critical to actin dynamics. Capping protein (CP) binds to barbed ends to prevent subunit gain and loss and is regulated by proteins that include V-1 and CARMIL. V-1 inhibits...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718306740 |
| _version_ | 1818425530769211392 |
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| author | Britney Johnson Patrick McConnell Alex G. Kozlov Marlene Mekel Timothy M. Lohman Michael L. Gross Gaya K. Amarasinghe John A. Cooper |
| author_facet | Britney Johnson Patrick McConnell Alex G. Kozlov Marlene Mekel Timothy M. Lohman Michael L. Gross Gaya K. Amarasinghe John A. Cooper |
| author_sort | Britney Johnson |
| collection | DOAJ |
| description | Actin assembly is important for cell motility. The ability of actin subunits to join or leave filaments via the barbed end is critical to actin dynamics. Capping protein (CP) binds to barbed ends to prevent subunit gain and loss and is regulated by proteins that include V-1 and CARMIL. V-1 inhibits CP by sterically blocking one binding site for actin. CARMILs bind at a distal site and decrease the affinity of CP for actin, suggested to be caused by conformational changes. We used hydrogen-deuterium exchange with mass spectrometry (HDX-MS) to probe changes in structural dynamics induced by V-1 and CARMIL binding to CP. V-1 and CARMIL induce changes in both proteins’ binding sites on the surface of CP, along with a set of internal residues. Both also affect the conformation of CP’s ββ subunit “tentacle,” a second distal actin-binding site. Concerted regulation of actin assembly by CP occurs through allosteric couplings between CP modulator and actin binding sites. |
| first_indexed | 2024-12-14T14:15:24Z |
| format | Article |
| id | doaj.art-f8380583d0ab4e5ea1829184075c0d34 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-14T14:15:24Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f8380583d0ab4e5ea1829184075c0d342022-12-21T22:58:13ZengElsevierCell Reports2211-12472018-05-012392795280410.1016/j.celrep.2018.04.096Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium ExchangeBritney Johnson0Patrick McConnell1Alex G. Kozlov2Marlene Mekel3Timothy M. Lohman4Michael L. Gross5Gaya K. Amarasinghe6John A. Cooper7Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USADepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USADepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USADepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USADepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USADepartment of Chemistry, Box 1134, Washington University, One Brookings Drive, St. Louis, MO 63130, USADepartment of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USADepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USAActin assembly is important for cell motility. The ability of actin subunits to join or leave filaments via the barbed end is critical to actin dynamics. Capping protein (CP) binds to barbed ends to prevent subunit gain and loss and is regulated by proteins that include V-1 and CARMIL. V-1 inhibits CP by sterically blocking one binding site for actin. CARMILs bind at a distal site and decrease the affinity of CP for actin, suggested to be caused by conformational changes. We used hydrogen-deuterium exchange with mass spectrometry (HDX-MS) to probe changes in structural dynamics induced by V-1 and CARMIL binding to CP. V-1 and CARMIL induce changes in both proteins’ binding sites on the surface of CP, along with a set of internal residues. Both also affect the conformation of CP’s ββ subunit “tentacle,” a second distal actin-binding site. Concerted regulation of actin assembly by CP occurs through allosteric couplings between CP modulator and actin binding sites.http://www.sciencedirect.com/science/article/pii/S2211124718306740allosteryactin regulationCARMILhydrogen-deuterium exchangemass spectrometry |
| spellingShingle | Britney Johnson Patrick McConnell Alex G. Kozlov Marlene Mekel Timothy M. Lohman Michael L. Gross Gaya K. Amarasinghe John A. Cooper Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange Cell Reports allostery actin regulation CARMIL hydrogen-deuterium exchange mass spectrometry |
| title | Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange |
| title_full | Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange |
| title_fullStr | Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange |
| title_full_unstemmed | Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange |
| title_short | Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange |
| title_sort | allosteric coupling of carmil and v 1 binding to capping protein revealed by hydrogen deuterium exchange |
| topic | allostery actin regulation CARMIL hydrogen-deuterium exchange mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718306740 |
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