Abstract
Peptide aptamers of LIM-only protein 2 (Lmo2) were previously used to successfully treat Lmo2-induced tumours in a mouse model of leukaemia. Here we show that the Lmo2 aptamer PA207, either as a free peptide or fused to thioredoxin Trx-PA207, causes purified Lmo2 to precipitate rather than binding to a defined surface on the protein. Stabilisation of Lmo2 through interaction with LIM domain binding protein 1 (Ldb1), a normal binding partner of Lmo2, abrogates this effect. The addition of free zinc causes Trx-PA207 to self associate, suggesting that PA207 destabilises Lmo2 by modulating normal zinc-coordination in the LIM domains. GST-pulldown experiments with other Lmo and Gata proteins indicates that PA207 can bind to a range of zinc finger proteins. Thus, PA207 and other cysteine-containing peptide aptamers for Lmo2 may form a class of general zinc finger inhibitors.
Keywords: Chemical shift perturbation experiments, Lmo2, peptide aptamer, peptide-protein interaction, protein destabilisation, zinc co-ordination.
Protein & Peptide Letters
Title:The PA207 Peptide Inhibitor of LIM-only Protein 2 (Lmo2) Targets Zinc Finger Domains in a Non-specific Manner
Volume: 21 Issue: 2
Author(s): Lorna Wilkinson-White and Jacqueline M. Matthews
Affiliation:
Keywords: Chemical shift perturbation experiments, Lmo2, peptide aptamer, peptide-protein interaction, protein destabilisation, zinc co-ordination.
Abstract: Peptide aptamers of LIM-only protein 2 (Lmo2) were previously used to successfully treat Lmo2-induced tumours in a mouse model of leukaemia. Here we show that the Lmo2 aptamer PA207, either as a free peptide or fused to thioredoxin Trx-PA207, causes purified Lmo2 to precipitate rather than binding to a defined surface on the protein. Stabilisation of Lmo2 through interaction with LIM domain binding protein 1 (Ldb1), a normal binding partner of Lmo2, abrogates this effect. The addition of free zinc causes Trx-PA207 to self associate, suggesting that PA207 destabilises Lmo2 by modulating normal zinc-coordination in the LIM domains. GST-pulldown experiments with other Lmo and Gata proteins indicates that PA207 can bind to a range of zinc finger proteins. Thus, PA207 and other cysteine-containing peptide aptamers for Lmo2 may form a class of general zinc finger inhibitors.
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Cite this article as:
Wilkinson-White Lorna and Matthews M. Jacqueline, The PA207 Peptide Inhibitor of LIM-only Protein 2 (Lmo2) Targets Zinc Finger Domains in a Non-specific Manner, Protein & Peptide Letters 2014; 21 (2) . https://dx.doi.org/10.2174/09298665113206660116
DOI https://dx.doi.org/10.2174/09298665113206660116 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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