Molecular characterization of direct interactions between MPP1 and flotillins

Abstract Flotillins are the major structural proteins in erythroid raft domains. We have shown previously that the dynamic nanoscale organization of raft domains in erythroid cells may depend on flotillin-MPP1 interactions. Here, by using molecular dynamic simulations and a surface plasmon resonance...

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Autores principales:	Agnieszka Biernatowska, Paulina Olszewska, Krzysztof Grzymajło, Dominik Drabik, Sebastian Kraszewski, Aleksander F. Sikorski, Aleksander Czogalla
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e62c81e730642f4a790ff25c2654fee
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spelling	oai:doaj.org-article:8e62c81e730642f4a790ff25c2654fee2021-12-02T17:03:50ZMolecular characterization of direct interactions between MPP1 and flotillins10.1038/s41598-021-93982-32045-2322https://doaj.org/article/8e62c81e730642f4a790ff25c2654fee2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93982-3https://doaj.org/toc/2045-2322Abstract Flotillins are the major structural proteins in erythroid raft domains. We have shown previously that the dynamic nanoscale organization of raft domains in erythroid cells may depend on flotillin-MPP1 interactions. Here, by using molecular dynamic simulations and a surface plasmon resonance-based approach we determined that high-affinity complexes of MPP1 and flotillins are formed via a so far unidentified region within the D5 domain of MPP1. Significantly, this particular “flotillin binding motif” is of key physiological importance, as overexpression of peptides containing this motif inhibited endogenous MPP1-flotillin interaction in erythroid precursor cells, thereby causing lateral disorganization of raft domains. This was reflected by both reduction in the plasma membrane order and markedly decreased activation of signal transduction via the raft-dependent insulin receptor pathway. Our data highlight new molecular details concerning the mechanism whereby MPP1 functionally links flotillins to exert their physiological role in raft domain formation.Agnieszka BiernatowskaPaulina OlszewskaKrzysztof GrzymajłoDominik DrabikSebastian KraszewskiAleksander F. SikorskiAleksander CzogallaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Agnieszka Biernatowska Paulina Olszewska Krzysztof Grzymajło Dominik Drabik Sebastian Kraszewski Aleksander F. Sikorski Aleksander Czogalla Molecular characterization of direct interactions between MPP1 and flotillins
description	Abstract Flotillins are the major structural proteins in erythroid raft domains. We have shown previously that the dynamic nanoscale organization of raft domains in erythroid cells may depend on flotillin-MPP1 interactions. Here, by using molecular dynamic simulations and a surface plasmon resonance-based approach we determined that high-affinity complexes of MPP1 and flotillins are formed via a so far unidentified region within the D5 domain of MPP1. Significantly, this particular “flotillin binding motif” is of key physiological importance, as overexpression of peptides containing this motif inhibited endogenous MPP1-flotillin interaction in erythroid precursor cells, thereby causing lateral disorganization of raft domains. This was reflected by both reduction in the plasma membrane order and markedly decreased activation of signal transduction via the raft-dependent insulin receptor pathway. Our data highlight new molecular details concerning the mechanism whereby MPP1 functionally links flotillins to exert their physiological role in raft domain formation.
format	article
author	Agnieszka Biernatowska Paulina Olszewska Krzysztof Grzymajło Dominik Drabik Sebastian Kraszewski Aleksander F. Sikorski Aleksander Czogalla
author_facet	Agnieszka Biernatowska Paulina Olszewska Krzysztof Grzymajło Dominik Drabik Sebastian Kraszewski Aleksander F. Sikorski Aleksander Czogalla
author_sort	Agnieszka Biernatowska
title	Molecular characterization of direct interactions between MPP1 and flotillins
title_short	Molecular characterization of direct interactions between MPP1 and flotillins
title_full	Molecular characterization of direct interactions between MPP1 and flotillins
title_fullStr	Molecular characterization of direct interactions between MPP1 and flotillins
title_full_unstemmed	Molecular characterization of direct interactions between MPP1 and flotillins
title_sort	molecular characterization of direct interactions between mpp1 and flotillins
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8e62c81e730642f4a790ff25c2654fee
work_keys_str_mv	AT agnieszkabiernatowska molecularcharacterizationofdirectinteractionsbetweenmpp1andflotillins AT paulinaolszewska molecularcharacterizationofdirectinteractionsbetweenmpp1andflotillins AT krzysztofgrzymajło molecularcharacterizationofdirectinteractionsbetweenmpp1andflotillins AT dominikdrabik molecularcharacterizationofdirectinteractionsbetweenmpp1andflotillins AT sebastiankraszewski molecularcharacterizationofdirectinteractionsbetweenmpp1andflotillins AT aleksanderfsikorski molecularcharacterizationofdirectinteractionsbetweenmpp1andflotillins AT aleksanderczogalla molecularcharacterizationofdirectinteractionsbetweenmpp1andflotillins
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Molecular characterization of direct interactions between MPP1 and flotillins

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