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Using Linear Motif Database Resources to Identify SH2 Domain Binders

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SH2 Domains

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2705))

Abstract

The SH2-binding phosphotyrosine class of short linear motifs (SLiMs) are key conditional regulatory elements, particularly in signaling protein complexes beneath the cell’s plasma membrane. In addition to transmitting cellular signaling information, they can also play roles in cellular hijack by invasive pathogens. Researchers can take advantage of bioinformatics tools and resources to predict the motifs at conserved phosphotyrosine residues in regions of intrinsically disordered protein. A candidate SH2-binding motif can be established and assigned to one or more of the SH2 domain subgroups. It is, however, not so straightforward to predict which SH2 domains are capable of binding the given candidate. This is largely due to the cooperative nature of the binding amino acids which enables poorer binding residues to be tolerated when the other residues are optimal. High-throughput peptide arrays are powerful tools used to derive SH2 domain-binding specificity, but they are unable to capture these cooperative effects and also suffer from other shortcomings. Tissue and cell type expression can help to restrict the list of available interactors: for example, some well-studied SH2 domain proteins are only present in the immune cell lineages. In this article, we provide a table of motif patterns and four bioinformatics strategies that introduce a range of tools that can be used in motif hunting in cellular and pathogen proteins. Experimental followup is essential to determine which SH2 domain/motif-containing proteins are the actual functional partners.

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Acknowledgments

L.B.C. is a National Research Council Investigator (CONICET, Argentina) and has received funding from Agencia Nacional de Promocion Cientifica y Tecnológica (ANPCyT) Grant #PICT-2017/1924 and #PICT-2019/02119. L.B.C. and T.J.G. received support from the European Union’s Horizon 2020 Marie Skłodowska-Curie action #778247 (IDPfun).

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Authors and Affiliations

  1. Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany

    Hugo Sámano-Sánchez, Toby J. Gibson & Lucía B. Chemes

  2. Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, China

    Hugo Sámano-Sánchez

  3. Biomedical Sciences, Edinburgh Medical School, The University of Edinburgh, Edinburgh, UK

    Hugo Sámano-Sánchez

  4. Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín, Argentina

    Lucía B. Chemes

  5. Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, San Martín, Argentina

    Lucía B. Chemes

Authors
  1. Hugo Sámano-Sánchez
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  2. Toby J. Gibson
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  3. Lucía B. Chemes
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Corresponding author

Correspondence to Lucía B. Chemes .

Editor information

Editors and Affiliations

  1. School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK

    Teresa Carlomagno

  2. Signalling Research Centres BIOSS &CIBSS, University of Freiburg, Freiburg, Germany

    Maja Köhn

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© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Sámano-Sánchez, H., Gibson, T.J., Chemes, L.B. (2023). Using Linear Motif Database Resources to Identify SH2 Domain Binders. In: Carlomagno, T., Köhn, M. (eds) SH2 Domains. Methods in Molecular Biology, vol 2705. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3393-9_9

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  • DOI: https://doi.org/10.1007/978-1-0716-3393-9_9

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3392-2

  • Online ISBN: 978-1-0716-3393-9

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