NMR-based homology model for the solution structure of the C-terminal globular domain of EMILIN1

Giuliana Verdone, Alessandra Corazza, Simon A. Colebrooke, Daniel Cicero, Tommaso Eliseo, Jonathan Boyd, Roberto Doliana, Federico Fogolari, Paolo Viglino, Alfonso Colombatti, Iain D. Campbell, Gennaro Esposito

    Research output: Contribution to journalArticle

    Abstract

    EMILIN1 is a glycoprotein of elastic tissues that has been recently linked to the pathogenesis of hypertension. The protein is formed by different independently folded structural domains whose role has been partially elucidated. In this paper the solution structure, inferred from NMR-based homology modelling of the C-terminal trimeric globular C1q domain (gC1q) of EMILIN1, is reported. The high molecular weight and the homotrimeric structure of the protein required the combined use of highly deuterated 15N, 13C-labelled samples and TROSY experiments. Starting from a homology model, the protein structure was refined using heteronuclear residual dipolar couplings, chemical shift patterns, NOEs and H-exchange data. Analysis of the gC1q domain structure of EMILIN1 shows that each protomer of the trimer adopts a nine-stranded β sandwich folding topology which is related to the conformation observed for other proteins of the family. Distinguishing features, however, include a missing edge-strand and an unstructured 19-residue loop. Although the current data do not allow this loop to be precisely defined, the available evidence is consistent with a flexible segment that protrudes from each subunit of the globular trimeric assembly and plays a key role in inter-molecular interactions between the EMILIN1 gC1q homotrimer and its integrin receptor α4β1.

    Original languageEnglish (US)
    Pages (from-to)79-96
    Number of pages18
    JournalJournal of Biomolecular NMR
    Volume43
    Issue number2
    DOIs
    StatePublished - Jan 1 2009

    Fingerprint

    Nuclear magnetic resonance
    Proteins
    Elastic Tissue
    Molecular interactions
    Protein Subunits
    Chemical shift
    Electronic data interchange
    Integrins
    Conformations
    Glycoproteins
    Molecular Weight
    Molecular weight
    Topology
    Tissue
    Hypertension
    Experiments

    Keywords

    • Elastic fibres
    • EMILIN1
    • Globular C1q domain
    • Homotrimeric proteins
    • Large system NMR
    • Partially deuterated proteins

    ASJC Scopus subject areas

    • Spectroscopy
    • Biochemistry

    Cite this

    Verdone, G., Corazza, A., Colebrooke, S. A., Cicero, D., Eliseo, T., Boyd, J., ... Esposito, G. (2009). NMR-based homology model for the solution structure of the C-terminal globular domain of EMILIN1. Journal of Biomolecular NMR, 43(2), 79-96. https://doi.org/10.1007/s10858-008-9290-y

    NMR-based homology model for the solution structure of the C-terminal globular domain of EMILIN1. / Verdone, Giuliana; Corazza, Alessandra; Colebrooke, Simon A.; Cicero, Daniel; Eliseo, Tommaso; Boyd, Jonathan; Doliana, Roberto; Fogolari, Federico; Viglino, Paolo; Colombatti, Alfonso; Campbell, Iain D.; Esposito, Gennaro.

    In: Journal of Biomolecular NMR, Vol. 43, No. 2, 01.01.2009, p. 79-96.

    Research output: Contribution to journalArticle

    Verdone, G, Corazza, A, Colebrooke, SA, Cicero, D, Eliseo, T, Boyd, J, Doliana, R, Fogolari, F, Viglino, P, Colombatti, A, Campbell, ID & Esposito, G 2009, 'NMR-based homology model for the solution structure of the C-terminal globular domain of EMILIN1', Journal of Biomolecular NMR, vol. 43, no. 2, pp. 79-96. https://doi.org/10.1007/s10858-008-9290-y
    Verdone, Giuliana ; Corazza, Alessandra ; Colebrooke, Simon A. ; Cicero, Daniel ; Eliseo, Tommaso ; Boyd, Jonathan ; Doliana, Roberto ; Fogolari, Federico ; Viglino, Paolo ; Colombatti, Alfonso ; Campbell, Iain D. ; Esposito, Gennaro. / NMR-based homology model for the solution structure of the C-terminal globular domain of EMILIN1. In: Journal of Biomolecular NMR. 2009 ; Vol. 43, No. 2. pp. 79-96.
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    AU - Cicero, Daniel

    AU - Eliseo, Tommaso

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    AU - Doliana, Roberto

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