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Structural and mutational studies suggest key residues to determine whether stomatin SPFH domains form dimers or trimers

Stomatin is a major integral membrane protein in human erythrocytes. In a form of hemolytic anemia known as hereditary stomatocytosis, stomatin is deficient in the erythrocyte membrane due to mis-trafficking. It is a member of stomatin, prohibitin, flotillin, and HflK/C (SPFH) domain proteins, and S...

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Autores principales: Komatsu, Tomoya, Matsui, Ikuo, Yokoyama, Hideshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663324/
https://www.ncbi.nlm.nih.gov/pubmed/36386441
http://dx.doi.org/10.1016/j.bbrep.2022.101384
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author Komatsu, Tomoya
Matsui, Ikuo
Yokoyama, Hideshi
author_facet Komatsu, Tomoya
Matsui, Ikuo
Yokoyama, Hideshi
author_sort Komatsu, Tomoya
collection PubMed
description Stomatin is a major integral membrane protein in human erythrocytes. In a form of hemolytic anemia known as hereditary stomatocytosis, stomatin is deficient in the erythrocyte membrane due to mis-trafficking. It is a member of stomatin, prohibitin, flotillin, and HflK/C (SPFH) domain proteins, and SPFH proteins could function as membrane-bound oligomeric scaffolding proteins in lipid rafts. The previously determined structure of the SPFH domain of Pyrococcus horikoshii (Ph) stomatin formed a trimer, whereas that of mouse stomatin formed a dimer. To elucidate the difference of oligomerization state, structural and chromatographic analyses using Ph stomatin were performed, and the key residues were suggested to determine whether SPFH domains form dimers or trimers. From gel-filtration analyses, PhStom (56–234) formed a trimer or tetramer, whereas PhStom (63–234) and PhStom (56–234) K59S formed a dimer. The residues 56–62, particularly Lys59, were involved in trimerization. Based on the crystal structure of PhStom (63–234), it formed a banana-shaped dimer, as observed in mouse stomatin. Thus, residues 162–168 are involved in dimerization. This study provides important insight into the molecular function and oligomerization state of stomatin.
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spelling pubmed-96633242022-11-15 Structural and mutational studies suggest key residues to determine whether stomatin SPFH domains form dimers or trimers Komatsu, Tomoya Matsui, Ikuo Yokoyama, Hideshi Biochem Biophys Rep Research Article Stomatin is a major integral membrane protein in human erythrocytes. In a form of hemolytic anemia known as hereditary stomatocytosis, stomatin is deficient in the erythrocyte membrane due to mis-trafficking. It is a member of stomatin, prohibitin, flotillin, and HflK/C (SPFH) domain proteins, and SPFH proteins could function as membrane-bound oligomeric scaffolding proteins in lipid rafts. The previously determined structure of the SPFH domain of Pyrococcus horikoshii (Ph) stomatin formed a trimer, whereas that of mouse stomatin formed a dimer. To elucidate the difference of oligomerization state, structural and chromatographic analyses using Ph stomatin were performed, and the key residues were suggested to determine whether SPFH domains form dimers or trimers. From gel-filtration analyses, PhStom (56–234) formed a trimer or tetramer, whereas PhStom (63–234) and PhStom (56–234) K59S formed a dimer. The residues 56–62, particularly Lys59, were involved in trimerization. Based on the crystal structure of PhStom (63–234), it formed a banana-shaped dimer, as observed in mouse stomatin. Thus, residues 162–168 are involved in dimerization. This study provides important insight into the molecular function and oligomerization state of stomatin. Elsevier 2022-11-11 /pmc/articles/PMC9663324/ /pubmed/36386441 http://dx.doi.org/10.1016/j.bbrep.2022.101384 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Komatsu, Tomoya
Matsui, Ikuo
Yokoyama, Hideshi
Structural and mutational studies suggest key residues to determine whether stomatin SPFH domains form dimers or trimers
title Structural and mutational studies suggest key residues to determine whether stomatin SPFH domains form dimers or trimers
title_full Structural and mutational studies suggest key residues to determine whether stomatin SPFH domains form dimers or trimers
title_fullStr Structural and mutational studies suggest key residues to determine whether stomatin SPFH domains form dimers or trimers
title_full_unstemmed Structural and mutational studies suggest key residues to determine whether stomatin SPFH domains form dimers or trimers
title_short Structural and mutational studies suggest key residues to determine whether stomatin SPFH domains form dimers or trimers
title_sort structural and mutational studies suggest key residues to determine whether stomatin spfh domains form dimers or trimers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663324/
https://www.ncbi.nlm.nih.gov/pubmed/36386441
http://dx.doi.org/10.1016/j.bbrep.2022.101384
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