title: The PA207 peptide inhibitor of LIM-only protein 2 (Lmo2) targets Zinc Finger domains in a non-specific manner.
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.
authors.forename: Lorna
authors.initials: L
authors.lastname: Wilkinson-White
authors.affiliation: School of Molecular Bioscience, University of Sydney, NSW 2006, Australia. jacqui.matthews@sydney.edu.au.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Matthews
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding / Q000187:drug effects; D013379:Substrate Specificity; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology; D016335:Zinc Fingers / Q000187:drug effects*
chemical_list: D004268:DNA-Binding Proteins; D010455:Peptides; D014157:Transcription Factors; D015032:Zinc