What's in the BAGs? Intrinsic disorder angle of the multifunctionality of the members of a family of chaperone regulators. Issue 1 (2nd August 2021)

• Record Type: Journal Article
• Authors: Marzullo, Liberato; Turco, Maria C.; Uversky, Vladimir N.
• Other Names: Rosati Alessandra guestEditor.; Turco Maria guestEditor.
• Is Part Of: Journal of cellular biochemistry. Volume 123:Issue 1(2022)
• Page Start: 22
• Page End: 42
• Publication Date: 2021-08-02
• Subjects: BAG proteins -- intrinsically disordered protein -- molecular recognition feature -- posttranslational modifications -- protein structure‐function continuum -- protein‐protein interaction -- proteoform; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.30123
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: In humans, the family of Bcl‐2 associated athanogene (BAG) proteins includes six members characterized by exceptional multifunctionality and engagement in the pathogenesis of various diseases. All of them are capable of interacting with a multitude of often unrelated binding partners. Such binding promiscuity and related functional and pathological multifacetedness cannot be explained or understood within the frames of the classical "one protein–one structure–one function" model, which also fails to explain the presence of multiple isoforms generated for BAG proteins by alternative splicing or alternative translation initiation and their extensive posttranslational modifications. However, all these mysteries can be solved by taking into account the intrinsic disorder phenomenon. In fact, high binding promiscuity and potential to participate in a broad spectrum of interactions with multiple binding partners, as well as a capability to be multifunctional and multipathogenic, are some of the characteristic features of intrinsically disordered proteins and intrinsically disordered protein regions. Such functional proteins or protein regions lacking unique tertiary structures constitute a cornerstone of the protein structure‐function continuum concept. The aim of this paper is to provide an overview of the functional roles of human BAG proteins from the perspective of protein intrinsic disorder which will provide a means for understanding their binding promiscuity, multifunctionality, and relation to the pathogenesis of various diseases. Abstract :