Accessing gap-junction channel structure-function relationships through molecular modeling and simulations

F. Villanelo, Y. Escalona, C. Pareja-Barrueto, J. A. Garate, I. M. Skerrett, T. Perez-Acle

Resultado de la investigación: Contribución a la publicaciónReview article

Resumen

Background: Gap junction channels (GJCs) are massive protein channels connecting the cytoplasm of adjacent cells. These channels allow intercellular transfer of molecules up to ~1 kDa, including water, ions and other metabolites. Unveiling structure-function relationships coded into the molecular architecture of these channels is necessary to gain insight on their vast biological function including electrical synapse, inflammation, development and tissular homeostasis. From early works, computational methods have been critical to analyze and interpret experimental observations. Upon the availability of crystallographic structures, molecular modeling and simulations have become a valuable tool to assess structure-function relationships in GJCs. Modeling different connexin isoforms, simulating the transport process, and exploring molecular variants, have provided new hypotheses and out-of-the-box approaches to the study of these important channels. Methods: Here, we review foundational structural studies and recent developments on GJCs using molecular modeling and simulation techniques, highlighting the methods and the cross-talk with experimental evidence. Results and discussion: By comparing results obtained by molecular modeling and simulations techniques with structural and functional information obtained from both recent literature and structural databases, we provide a critical assesment of structure-function relationships that can be obtained from the junction between theoretical and experimental evidence.

Idioma originalEnglish
Número de artículo5
PublicaciónBMC Cell Biology
Volumen18
Identificadores de objetos digitales
EstadoPublished - 17 ene 2017

Huella dactilar

Gap Junctions
Connexins
Electrical Synapses
Molecular Structure
Protein Isoforms
Cytoplasm
Homeostasis
Ions
Inflammation
Water

Keywords

    ASJC Scopus subject areas

    • Cell Biology

    Citar esto

    Villanelo, F., Escalona, Y., Pareja-Barrueto, C., Garate, J. A., Skerrett, I. M., & Perez-Acle, T. (2017). Accessing gap-junction channel structure-function relationships through molecular modeling and simulations. BMC Cell Biology, 18, [5]. DOI: 10.1186/s12860-016-0121-9

    Villanelo, F.; Escalona, Y.; Pareja-Barrueto, C.; Garate, J. A.; Skerrett, I. M.; Perez-Acle, T. / Accessing gap-junction channel structure-function relationships through molecular modeling and simulations.

    En: BMC Cell Biology, Vol. 18, 5, 17.01.2017.

    Resultado de la investigación: Contribución a la publicaciónReview article

    @article{133ac064d3164db192fd0f799d2a1db3,
    title = "Accessing gap-junction channel structure-function relationships through molecular modeling and simulations",
    abstract = "Background: Gap junction channels (GJCs) are massive protein channels connecting the cytoplasm of adjacent cells. These channels allow intercellular transfer of molecules up to ~1 kDa, including water, ions and other metabolites. Unveiling structure-function relationships coded into the molecular architecture of these channels is necessary to gain insight on their vast biological function including electrical synapse, inflammation, development and tissular homeostasis. From early works, computational methods have been critical to analyze and interpret experimental observations. Upon the availability of crystallographic structures, molecular modeling and simulations have become a valuable tool to assess structure-function relationships in GJCs. Modeling different connexin isoforms, simulating the transport process, and exploring molecular variants, have provided new hypotheses and out-of-the-box approaches to the study of these important channels. Methods: Here, we review foundational structural studies and recent developments on GJCs using molecular modeling and simulation techniques, highlighting the methods and the cross-talk with experimental evidence. Results and discussion: By comparing results obtained by molecular modeling and simulations techniques with structural and functional information obtained from both recent literature and structural databases, we provide a critical assesment of structure-function relationships that can be obtained from the junction between theoretical and experimental evidence.",
    keywords = "Connexins, Gap-junction channels, Hemichannels, Homology modeling, Molecular simulation, Structure and function",
    author = "F. Villanelo and Y. Escalona and C. Pareja-Barrueto and Garate, {J. A.} and Skerrett, {I. M.} and T. Perez-Acle",
    year = "2017",
    month = "1",
    doi = "10.1186/s12860-016-0121-9",
    volume = "18",
    journal = "BMC Cell Biology",
    issn = "1471-2121",
    publisher = "BioMed Central",

    }

    Villanelo, F, Escalona, Y, Pareja-Barrueto, C, Garate, JA, Skerrett, IM & Perez-Acle, T 2017, 'Accessing gap-junction channel structure-function relationships through molecular modeling and simulations' BMC Cell Biology, vol. 18, 5. DOI: 10.1186/s12860-016-0121-9

    Accessing gap-junction channel structure-function relationships through molecular modeling and simulations. / Villanelo, F.; Escalona, Y.; Pareja-Barrueto, C.; Garate, J. A.; Skerrett, I. M.; Perez-Acle, T.

    En: BMC Cell Biology, Vol. 18, 5, 17.01.2017.

    Resultado de la investigación: Contribución a la publicaciónReview article

    TY - JOUR

    T1 - Accessing gap-junction channel structure-function relationships through molecular modeling and simulations

    AU - Villanelo,F.

    AU - Escalona,Y.

    AU - Pareja-Barrueto,C.

    AU - Garate,J. A.

    AU - Skerrett,I. M.

    AU - Perez-Acle,T.

    PY - 2017/1/17

    Y1 - 2017/1/17

    N2 - Background: Gap junction channels (GJCs) are massive protein channels connecting the cytoplasm of adjacent cells. These channels allow intercellular transfer of molecules up to ~1 kDa, including water, ions and other metabolites. Unveiling structure-function relationships coded into the molecular architecture of these channels is necessary to gain insight on their vast biological function including electrical synapse, inflammation, development and tissular homeostasis. From early works, computational methods have been critical to analyze and interpret experimental observations. Upon the availability of crystallographic structures, molecular modeling and simulations have become a valuable tool to assess structure-function relationships in GJCs. Modeling different connexin isoforms, simulating the transport process, and exploring molecular variants, have provided new hypotheses and out-of-the-box approaches to the study of these important channels. Methods: Here, we review foundational structural studies and recent developments on GJCs using molecular modeling and simulation techniques, highlighting the methods and the cross-talk with experimental evidence. Results and discussion: By comparing results obtained by molecular modeling and simulations techniques with structural and functional information obtained from both recent literature and structural databases, we provide a critical assesment of structure-function relationships that can be obtained from the junction between theoretical and experimental evidence.

    AB - Background: Gap junction channels (GJCs) are massive protein channels connecting the cytoplasm of adjacent cells. These channels allow intercellular transfer of molecules up to ~1 kDa, including water, ions and other metabolites. Unveiling structure-function relationships coded into the molecular architecture of these channels is necessary to gain insight on their vast biological function including electrical synapse, inflammation, development and tissular homeostasis. From early works, computational methods have been critical to analyze and interpret experimental observations. Upon the availability of crystallographic structures, molecular modeling and simulations have become a valuable tool to assess structure-function relationships in GJCs. Modeling different connexin isoforms, simulating the transport process, and exploring molecular variants, have provided new hypotheses and out-of-the-box approaches to the study of these important channels. Methods: Here, we review foundational structural studies and recent developments on GJCs using molecular modeling and simulation techniques, highlighting the methods and the cross-talk with experimental evidence. Results and discussion: By comparing results obtained by molecular modeling and simulations techniques with structural and functional information obtained from both recent literature and structural databases, we provide a critical assesment of structure-function relationships that can be obtained from the junction between theoretical and experimental evidence.

    KW - Connexins

    KW - Gap-junction channels

    KW - Hemichannels

    KW - Homology modeling

    KW - Molecular simulation

    KW - Structure and function

    UR - http://www.scopus.com/inward/record.url?scp=85010002027&partnerID=8YFLogxK

    U2 - 10.1186/s12860-016-0121-9

    DO - 10.1186/s12860-016-0121-9

    M3 - Review article

    VL - 18

    JO - BMC Cell Biology

    T2 - BMC Cell Biology

    JF - BMC Cell Biology

    SN - 1471-2121

    M1 - 5

    ER -

    Villanelo F, Escalona Y, Pareja-Barrueto C, Garate JA, Skerrett IM, Perez-Acle T. Accessing gap-junction channel structure-function relationships through molecular modeling and simulations. BMC Cell Biology. 2017 ene 17;18. 5. Disponible desde, DOI: 10.1186/s12860-016-0121-9