Unraveling the Membrane Topology of TMEM151A: A Step Towards Understanding its Cellular Role
[Display omitted] •TMEM151A has a transmembrane domain and a large intracellular domain.•TMEM151A transmembrane domain has helix-hinge-helix motif.•TMEM151A intracellular domain has β-hairpin motif.•TMEM151A is localized also at the plasma membrane. Transmembrane protein 151A (TMEM151A) has been ide...
Gespeichert in:
Veröffentlicht in: | Journal of molecular biology 2024-12, Vol.436 (23), p.168834, Article 168834 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 23 |
container_start_page | 168834 |
container_title | Journal of molecular biology |
container_volume | 436 |
creator | Morinelli, Lisastella Corradi, Beatrice Arnaldi, Pietro Cortese, Katia Muià, Martina Zara, Federico Maragliano, Luca Sterlini, Bruno Corradi, Anna |
description | [Display omitted]
•TMEM151A has a transmembrane domain and a large intracellular domain.•TMEM151A transmembrane domain has helix-hinge-helix motif.•TMEM151A intracellular domain has β-hairpin motif.•TMEM151A is localized also at the plasma membrane.
Transmembrane protein 151A (TMEM151A) has been identified as a causative gene for paroxysmal kinesigenic dyskinesia, though its molecular function remains almost completely unknown. Understanding the membrane topology of transmembrane proteins is crucial for elucidating their functions and possible interacting partners. In this study, we utilized molecular dynamics simulations, immunocytochemistry, and electron microscopy to define the topology of TMEM151A. Our results validate a starting AlphaFold model of TMEM151A and reveal that it comprises a transmembrane domain with two membrane-spanning alpha helices connected by a short extracellular loop and an intramembrane helix-hinge-helix structure. Notably, most of the protein is oriented towards the intracellular side of the membranes with a large cytosolic domain featuring a combination of alpha-helix and beta-sheet structures, as well as the protein N- and C-termini. These insights into TMEM151A’s topology and orientation of its domains with respect of the cell membranes provide essential information for future functional studies and represent a first fundamental step for understanding its role in the pathogenesis of paroxysmal kinesigenic dyskinesia. |
doi_str_mv | 10.1016/j.jmb.2024.168834 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3121058990</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0022283624004637</els_id><sourcerecordid>3121058990</sourcerecordid><originalsourceid>FETCH-LOGICAL-c235t-ec490a5a3f62e82fcc9f70ec5d1faf1874ba9371250ef1f23d4c3824f8dcc7873</originalsourceid><addsrcrecordid>eNp9kMtOwzAQRS0EoqXwAWyQl2xS_EriwKqqeEmtkKDdIVmuPS6pkrjYKah_T6oWlqxmMedezRyELikZUkKzm9VwVS-GjDAxpJmUXByhPiWySGTG5THqE8JYwiTPeugsxhUhJOVCnqIeL0QqcpH30fu8CfoLqrJZ4vYD8BTqRdAN4Jlf-8ovt9g7PJveT2lKR7d4hN9aWHfLbx1sxPPGQoitbuwuX7YRj6GqNpUO-NVXcI5OnK4iXBzmAM0f7mfjp2Ty8vg8Hk0Sw3jaJmBEQXSqucsYSOaMKVxOwKSWOu2ozMVCFzynLCXgqGPcCsMlE05aY3KZ8wG63veug__cQGxVXUbTXdI94jdRccooSWVRkA6le9QEH2MAp9ahrHXYKkrUTqpaqU6q2klVe6ld5upQv1nUYP8SvxY74G4PQPfkVwlBRVNCY8CWAUyrrC__qf8BXm2Glw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3121058990</pqid></control><display><type>article</type><title>Unraveling the Membrane Topology of TMEM151A: A Step Towards Understanding its Cellular Role</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Morinelli, Lisastella ; Corradi, Beatrice ; Arnaldi, Pietro ; Cortese, Katia ; Muià, Martina ; Zara, Federico ; Maragliano, Luca ; Sterlini, Bruno ; Corradi, Anna</creator><creatorcontrib>Morinelli, Lisastella ; Corradi, Beatrice ; Arnaldi, Pietro ; Cortese, Katia ; Muià, Martina ; Zara, Federico ; Maragliano, Luca ; Sterlini, Bruno ; Corradi, Anna</creatorcontrib><description>[Display omitted]
•TMEM151A has a transmembrane domain and a large intracellular domain.•TMEM151A transmembrane domain has helix-hinge-helix motif.•TMEM151A intracellular domain has β-hairpin motif.•TMEM151A is localized also at the plasma membrane.
Transmembrane protein 151A (TMEM151A) has been identified as a causative gene for paroxysmal kinesigenic dyskinesia, though its molecular function remains almost completely unknown. Understanding the membrane topology of transmembrane proteins is crucial for elucidating their functions and possible interacting partners. In this study, we utilized molecular dynamics simulations, immunocytochemistry, and electron microscopy to define the topology of TMEM151A. Our results validate a starting AlphaFold model of TMEM151A and reveal that it comprises a transmembrane domain with two membrane-spanning alpha helices connected by a short extracellular loop and an intramembrane helix-hinge-helix structure. Notably, most of the protein is oriented towards the intracellular side of the membranes with a large cytosolic domain featuring a combination of alpha-helix and beta-sheet structures, as well as the protein N- and C-termini. These insights into TMEM151A’s topology and orientation of its domains with respect of the cell membranes provide essential information for future functional studies and represent a first fundamental step for understanding its role in the pathogenesis of paroxysmal kinesigenic dyskinesia.</description><identifier>ISSN: 0022-2836</identifier><identifier>ISSN: 1089-8638</identifier><identifier>EISSN: 1089-8638</identifier><identifier>DOI: 10.1016/j.jmb.2024.168834</identifier><identifier>PMID: 39454747</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Cell Membrane - metabolism ; Humans ; Immunohistochemistry ; Membrane Proteins - chemistry ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Microscopy, Electron ; Models, Molecular ; Molecular Dynamics Simulation ; paroxysmal kinesigenic dyskinesia ; Protein Conformation ; Protein Structure, Secondary ; protein topology ; TMEM151A ; transmembrane protein</subject><ispartof>Journal of molecular biology, 2024-12, Vol.436 (23), p.168834, Article 168834</ispartof><rights>2024</rights><rights>Copyright © 2024. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c235t-ec490a5a3f62e82fcc9f70ec5d1faf1874ba9371250ef1f23d4c3824f8dcc7873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jmb.2024.168834$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39454747$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morinelli, Lisastella</creatorcontrib><creatorcontrib>Corradi, Beatrice</creatorcontrib><creatorcontrib>Arnaldi, Pietro</creatorcontrib><creatorcontrib>Cortese, Katia</creatorcontrib><creatorcontrib>Muià, Martina</creatorcontrib><creatorcontrib>Zara, Federico</creatorcontrib><creatorcontrib>Maragliano, Luca</creatorcontrib><creatorcontrib>Sterlini, Bruno</creatorcontrib><creatorcontrib>Corradi, Anna</creatorcontrib><title>Unraveling the Membrane Topology of TMEM151A: A Step Towards Understanding its Cellular Role</title><title>Journal of molecular biology</title><addtitle>J Mol Biol</addtitle><description>[Display omitted]
•TMEM151A has a transmembrane domain and a large intracellular domain.•TMEM151A transmembrane domain has helix-hinge-helix motif.•TMEM151A intracellular domain has β-hairpin motif.•TMEM151A is localized also at the plasma membrane.
Transmembrane protein 151A (TMEM151A) has been identified as a causative gene for paroxysmal kinesigenic dyskinesia, though its molecular function remains almost completely unknown. Understanding the membrane topology of transmembrane proteins is crucial for elucidating their functions and possible interacting partners. In this study, we utilized molecular dynamics simulations, immunocytochemistry, and electron microscopy to define the topology of TMEM151A. Our results validate a starting AlphaFold model of TMEM151A and reveal that it comprises a transmembrane domain with two membrane-spanning alpha helices connected by a short extracellular loop and an intramembrane helix-hinge-helix structure. Notably, most of the protein is oriented towards the intracellular side of the membranes with a large cytosolic domain featuring a combination of alpha-helix and beta-sheet structures, as well as the protein N- and C-termini. These insights into TMEM151A’s topology and orientation of its domains with respect of the cell membranes provide essential information for future functional studies and represent a first fundamental step for understanding its role in the pathogenesis of paroxysmal kinesigenic dyskinesia.</description><subject>Cell Membrane - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Membrane Proteins - chemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Microscopy, Electron</subject><subject>Models, Molecular</subject><subject>Molecular Dynamics Simulation</subject><subject>paroxysmal kinesigenic dyskinesia</subject><subject>Protein Conformation</subject><subject>Protein Structure, Secondary</subject><subject>protein topology</subject><subject>TMEM151A</subject><subject>transmembrane protein</subject><issn>0022-2836</issn><issn>1089-8638</issn><issn>1089-8638</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EoqXwAWyQl2xS_EriwKqqeEmtkKDdIVmuPS6pkrjYKah_T6oWlqxmMedezRyELikZUkKzm9VwVS-GjDAxpJmUXByhPiWySGTG5THqE8JYwiTPeugsxhUhJOVCnqIeL0QqcpH30fu8CfoLqrJZ4vYD8BTqRdAN4Jlf-8ovt9g7PJveT2lKR7d4hN9aWHfLbx1sxPPGQoitbuwuX7YRj6GqNpUO-NVXcI5OnK4iXBzmAM0f7mfjp2Ty8vg8Hk0Sw3jaJmBEQXSqucsYSOaMKVxOwKSWOu2ozMVCFzynLCXgqGPcCsMlE05aY3KZ8wG63veug__cQGxVXUbTXdI94jdRccooSWVRkA6le9QEH2MAp9ahrHXYKkrUTqpaqU6q2klVe6ld5upQv1nUYP8SvxY74G4PQPfkVwlBRVNCY8CWAUyrrC__qf8BXm2Glw</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Morinelli, Lisastella</creator><creator>Corradi, Beatrice</creator><creator>Arnaldi, Pietro</creator><creator>Cortese, Katia</creator><creator>Muià, Martina</creator><creator>Zara, Federico</creator><creator>Maragliano, Luca</creator><creator>Sterlini, Bruno</creator><creator>Corradi, Anna</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20241201</creationdate><title>Unraveling the Membrane Topology of TMEM151A: A Step Towards Understanding its Cellular Role</title><author>Morinelli, Lisastella ; Corradi, Beatrice ; Arnaldi, Pietro ; Cortese, Katia ; Muià, Martina ; Zara, Federico ; Maragliano, Luca ; Sterlini, Bruno ; Corradi, Anna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c235t-ec490a5a3f62e82fcc9f70ec5d1faf1874ba9371250ef1f23d4c3824f8dcc7873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Cell Membrane - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Membrane Proteins - chemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Microscopy, Electron</topic><topic>Models, Molecular</topic><topic>Molecular Dynamics Simulation</topic><topic>paroxysmal kinesigenic dyskinesia</topic><topic>Protein Conformation</topic><topic>Protein Structure, Secondary</topic><topic>protein topology</topic><topic>TMEM151A</topic><topic>transmembrane protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morinelli, Lisastella</creatorcontrib><creatorcontrib>Corradi, Beatrice</creatorcontrib><creatorcontrib>Arnaldi, Pietro</creatorcontrib><creatorcontrib>Cortese, Katia</creatorcontrib><creatorcontrib>Muià, Martina</creatorcontrib><creatorcontrib>Zara, Federico</creatorcontrib><creatorcontrib>Maragliano, Luca</creatorcontrib><creatorcontrib>Sterlini, Bruno</creatorcontrib><creatorcontrib>Corradi, Anna</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morinelli, Lisastella</au><au>Corradi, Beatrice</au><au>Arnaldi, Pietro</au><au>Cortese, Katia</au><au>Muià, Martina</au><au>Zara, Federico</au><au>Maragliano, Luca</au><au>Sterlini, Bruno</au><au>Corradi, Anna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unraveling the Membrane Topology of TMEM151A: A Step Towards Understanding its Cellular Role</atitle><jtitle>Journal of molecular biology</jtitle><addtitle>J Mol Biol</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>436</volume><issue>23</issue><spage>168834</spage><pages>168834-</pages><artnum>168834</artnum><issn>0022-2836</issn><issn>1089-8638</issn><eissn>1089-8638</eissn><abstract>[Display omitted]
•TMEM151A has a transmembrane domain and a large intracellular domain.•TMEM151A transmembrane domain has helix-hinge-helix motif.•TMEM151A intracellular domain has β-hairpin motif.•TMEM151A is localized also at the plasma membrane.
Transmembrane protein 151A (TMEM151A) has been identified as a causative gene for paroxysmal kinesigenic dyskinesia, though its molecular function remains almost completely unknown. Understanding the membrane topology of transmembrane proteins is crucial for elucidating their functions and possible interacting partners. In this study, we utilized molecular dynamics simulations, immunocytochemistry, and electron microscopy to define the topology of TMEM151A. Our results validate a starting AlphaFold model of TMEM151A and reveal that it comprises a transmembrane domain with two membrane-spanning alpha helices connected by a short extracellular loop and an intramembrane helix-hinge-helix structure. Notably, most of the protein is oriented towards the intracellular side of the membranes with a large cytosolic domain featuring a combination of alpha-helix and beta-sheet structures, as well as the protein N- and C-termini. These insights into TMEM151A’s topology and orientation of its domains with respect of the cell membranes provide essential information for future functional studies and represent a first fundamental step for understanding its role in the pathogenesis of paroxysmal kinesigenic dyskinesia.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>39454747</pmid><doi>10.1016/j.jmb.2024.168834</doi></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0022-2836 |
ispartof | Journal of molecular biology, 2024-12, Vol.436 (23), p.168834, Article 168834 |
issn | 0022-2836 1089-8638 1089-8638 |
language | eng |
recordid | cdi_proquest_miscellaneous_3121058990 |
source | MEDLINE; Access via ScienceDirect (Elsevier) |
subjects | Cell Membrane - metabolism Humans Immunohistochemistry Membrane Proteins - chemistry Membrane Proteins - genetics Membrane Proteins - metabolism Microscopy, Electron Models, Molecular Molecular Dynamics Simulation paroxysmal kinesigenic dyskinesia Protein Conformation Protein Structure, Secondary protein topology TMEM151A transmembrane protein |
title | Unraveling the Membrane Topology of TMEM151A: A Step Towards Understanding its Cellular Role |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T03%3A11%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Unraveling%20the%20Membrane%20Topology%20of%20TMEM151A:%20A%20Step%20Towards%20Understanding%20its%20Cellular%20Role&rft.jtitle=Journal%20of%20molecular%20biology&rft.au=Morinelli,%20Lisastella&rft.date=2024-12-01&rft.volume=436&rft.issue=23&rft.spage=168834&rft.pages=168834-&rft.artnum=168834&rft.issn=0022-2836&rft.eissn=1089-8638&rft_id=info:doi/10.1016/j.jmb.2024.168834&rft_dat=%3Cproquest_cross%3E3121058990%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3121058990&rft_id=info:pmid/39454747&rft_els_id=S0022283624004637&rfr_iscdi=true |