Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners

By Christopher J. Oldfield, Jingwei Meng, Jack Y. Yang, M. Yang, Vladimir N Uversky, A. Keith Dunker. BMC Genomics, 2008

594 citations recorded by the source corpus.

BackgroundProteins are involved in many interactions with other proteins leading to networks that regulate and control a wide variety of physiological processes. Some of these proteins, called hub proteins or hubs, bind to many different protein partners. Protein intrinsic disorder, via diversity arising from structural plasticity or flexibility, provide a means for hubs to associate with many partners (Dunker AK, Cortese MS, Romero P, Iakoucheva LM, Uversky VN: Flexible Nets: The roles of intrinsic disorder in protein interaction networks. FEBS J 2005, 272:5129-5148).ResultsHere we present a detailed examination of two divergent examples: 1) p53, which uses different disordered regions to bind to different partners and which also has several individual disordered regions that each bind to multiple partners, and 2) 14-3-3, which is a structured protein that associates with many different intrinsically disordered partners. For both examples, three-dimensional structures of multiple complexes reveal that the flexibility and plasticity of intrinsically disordered protein regions as well as induced-fit changes in the structured regions are both important for binding diversity.ConclusionsThese data support the conjecture that hub proteins often utilize intrinsic disorder to bind to multiple partners and provide detailed information about induced fit in structured regions.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2308234a989ef3e6f42ed3a11c20df194b672d7d

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Citations in the corpus

Linking Folding and Binding (2009, background): “Examples include the intrinsically disordered regulatory region near the C-terminus of p53, which folds into helical, b-strand, and extended irregular structures on binding to different protein partners [26], and the C-terminal activation domain of the hypoxia inducible factor HIF-1a which adopts he”
Prediction of Protein Binding Regions in Disordered Proteins (2009, background): “In a different scenario, the binding partners of an ordered protein are disordered, as shown for binding of 14-3-3 proteins, thus allowing a single protein to bind multiple partners [32].”
Intrinsically Disordered Proteins and Their “Mysterious” (Meta)Physics (2019, background): “Many IDPs/IDPRs serve as morphing shape-changers that are able to differently fold as a result of binding to different partners [56, 87, 135, 142–144], with the binding region of such a morphing IDP adopting completely different structures in the rigidified assemblies formed by the binding to diverg”
p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure–Function Continuum Concept (2016, background): “Although this domain is structured, it folds during the tetramerization process and the show structure is acquired upon the formation of the complex [30].”
Intrinsically Disordered Proteins Studied by NMR Spectroscopy (2015, background): “On the other hand, there are many examples of IDPs and IDP regions that bind to different partners and fold differently when they bind to the different partners (Oldfield et al. 2008; Hsu et al. 2013) just as suggested earlier (Rothen and Landsteiner 1939; Pauling 1940).”
A decade and a half of protein intrinsic disorder: Biology still waits for physics (2013, background): “bind to multiple partners gaining very different structures in the bound state.(77)”
How Random are Intrinsically Disordered Proteins? A Small Angle Scattering Perspective (2012, background): “Most of them participate in intricate interaction networks and are implicated in molecular recognition processes with multiple partners [5, 6], sometimes through an induced folding mechanism, in which the disordered protein gains secondary structural elements upon binding to its partner [7].”
The roles of conditional disorder in redox proteins (2013, background): “The involvement of intrinsic plasticity in molecular recognition is often explained in terms of promiscuity and flexibility [5,27,55,56].”