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Structural insights into kinetoplastid coronin oligomerization domain and F-actin interaction

The two-domain actin associated protein coronin interacts with filamentous (F-) actin, facilitating diverse biological processes including cell proliferation, motility, phagocytosis, host-parasite interaction and cargo binding. The conserved N-terminal β-propeller domain is involved in protein: prot...

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Autores principales: Parihar, Pankaj Singh, Singh, Aastha, Karade, Sharanbasappa Shrimant, Sahasrabuddhe, Amogh Anant, Pratap, J. Venkatesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554105/
https://www.ncbi.nlm.nih.gov/pubmed/34746809
http://dx.doi.org/10.1016/j.crstbi.2021.10.002
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author Parihar, Pankaj Singh
Singh, Aastha
Karade, Sharanbasappa Shrimant
Sahasrabuddhe, Amogh Anant
Pratap, J. Venkatesh
author_facet Parihar, Pankaj Singh
Singh, Aastha
Karade, Sharanbasappa Shrimant
Sahasrabuddhe, Amogh Anant
Pratap, J. Venkatesh
author_sort Parihar, Pankaj Singh
collection PubMed
description The two-domain actin associated protein coronin interacts with filamentous (F-) actin, facilitating diverse biological processes including cell proliferation, motility, phagocytosis, host-parasite interaction and cargo binding. The conserved N-terminal β-propeller domain is involved in protein: protein interactions, while the C-terminal coiled-coil domain mediates oligomerization, transducing conformational changes. The L. donovani coronin coiled-coil (LdCoroCC) domain exhibited a novel topology and oligomer association with an inherent asymmetry, caused primarily by three a residues of successive heptads. In the T.brucei homolog (TbrCoro), two of these ‘a’ residues are different (Val 493 & 507 replacing LdCoroCC Ile 486 and Met 500 respectively). The elucidated structure possesses a similar topology and assembly while comparative structural analysis shows that the T.brucei coronin coiled-coil domain (TbrCoroCC) too possesses the asymmetry though its magnitude is smaller. Analysis identifies that the asymmetric state is stabilized via cyclic salt bridges formed by Arg 497 and Glu 504. Co-localization studies (LdCoro, TbrCoro and corresponding mutant coiled coil constructs) with actin show that there are subtle differences in their binding patterns, with the double mutant V493I–V507M showing maximal effect. None of the constructs have an effect on F-actin length. Taken together with LdCoroCC, we therefore conclude that the inherent asymmetric structures are essential for kinetoplastids, and are of interest in understanding and exploiting actin dynamics.
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spelling pubmed-85541052021-11-04 Structural insights into kinetoplastid coronin oligomerization domain and F-actin interaction Parihar, Pankaj Singh Singh, Aastha Karade, Sharanbasappa Shrimant Sahasrabuddhe, Amogh Anant Pratap, J. Venkatesh Curr Res Struct Biol Research Article The two-domain actin associated protein coronin interacts with filamentous (F-) actin, facilitating diverse biological processes including cell proliferation, motility, phagocytosis, host-parasite interaction and cargo binding. The conserved N-terminal β-propeller domain is involved in protein: protein interactions, while the C-terminal coiled-coil domain mediates oligomerization, transducing conformational changes. The L. donovani coronin coiled-coil (LdCoroCC) domain exhibited a novel topology and oligomer association with an inherent asymmetry, caused primarily by three a residues of successive heptads. In the T.brucei homolog (TbrCoro), two of these ‘a’ residues are different (Val 493 & 507 replacing LdCoroCC Ile 486 and Met 500 respectively). The elucidated structure possesses a similar topology and assembly while comparative structural analysis shows that the T.brucei coronin coiled-coil domain (TbrCoroCC) too possesses the asymmetry though its magnitude is smaller. Analysis identifies that the asymmetric state is stabilized via cyclic salt bridges formed by Arg 497 and Glu 504. Co-localization studies (LdCoro, TbrCoro and corresponding mutant coiled coil constructs) with actin show that there are subtle differences in their binding patterns, with the double mutant V493I–V507M showing maximal effect. None of the constructs have an effect on F-actin length. Taken together with LdCoroCC, we therefore conclude that the inherent asymmetric structures are essential for kinetoplastids, and are of interest in understanding and exploiting actin dynamics. Elsevier 2021-10-14 /pmc/articles/PMC8554105/ /pubmed/34746809 http://dx.doi.org/10.1016/j.crstbi.2021.10.002 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Parihar, Pankaj Singh
Singh, Aastha
Karade, Sharanbasappa Shrimant
Sahasrabuddhe, Amogh Anant
Pratap, J. Venkatesh
Structural insights into kinetoplastid coronin oligomerization domain and F-actin interaction
title Structural insights into kinetoplastid coronin oligomerization domain and F-actin interaction
title_full Structural insights into kinetoplastid coronin oligomerization domain and F-actin interaction
title_fullStr Structural insights into kinetoplastid coronin oligomerization domain and F-actin interaction
title_full_unstemmed Structural insights into kinetoplastid coronin oligomerization domain and F-actin interaction
title_short Structural insights into kinetoplastid coronin oligomerization domain and F-actin interaction
title_sort structural insights into kinetoplastid coronin oligomerization domain and f-actin interaction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554105/
https://www.ncbi.nlm.nih.gov/pubmed/34746809
http://dx.doi.org/10.1016/j.crstbi.2021.10.002
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