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Molecular Medicine Faculty Publications

Protein function

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Networks Of Networks: An Essay On Multi-Level Biological Organization, Vladimir N. Uversky, Alessandro Giuliani Jan 2021

Networks Of Networks: An Essay On Multi-Level Biological Organization, Vladimir N. Uversky, Alessandro Giuliani

Molecular Medicine Faculty Publications

The multi-level organization of nature is self-evident: proteins do interact among them to give rise to an organized metabolism, while in the same time each protein (a single node of such interaction network) is itself a network of interacting amino-acid residues allowing coordinated motion of the macromolecule and systemic effect as allosteric behavior. Similar pictures can be drawn for structure and function of cells, organs, tissues, and ecological systems. The majority of biologists are used to think that causally relevant events originate from the lower level (the molecular one) in the form of perturbations, that “climb up” the hierarchy reaching …


New Technologies To Analyse Protein Function: An Intrinsic Disorder Perspective, Vladimir N. Uversky Jan 2020

New Technologies To Analyse Protein Function: An Intrinsic Disorder Perspective, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Functions of intrinsically disordered proteins do not require structure. Such structure-independent functionality has melted away the classic rigid “lock and key” representation of structure–function relationships in proteins, opening a new page in protein science, where molten keys operate on melted locks and where conformational flexibility and intrinsic disorder, structural plasticity and extreme malleability, multifunctionality and binding promiscuity represent a new-fangled reality. Analysis and understanding of this new reality require novel tools, and some of the techniques elaborated for the examination of intrinsically disordered protein functions are outlined in this review.


Intrinsically Disordered Proteins In The Nucleus Of Human Cells, Telma Frege, Vladimir N. Uversky Jan 2015

Intrinsically Disordered Proteins In The Nucleus Of Human Cells, Telma Frege, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Intrinsically disordered proteins are known to perform a variety of important functions such as macromolecular recognition, promiscuous binding, and signaling. They are crucial players in various cellular pathway and processes, where they often have key regulatory roles. Among vital cellular processes intimately linked to the intrinsically disordered proteins is transcription, an intricate biological performance predominantly developing inside the cell nucleus. With this work, we gathered information about proteins that exist in various compartments and sub-nuclear bodies of the nucleus of the human cells, with the goal of identifying which ones are highly disordered and which functions are ascribed to the …


Malleable Ribonucleoprotein Machine: Protein Intrinsic Disorder In The Saccharomyces Cerevisiae Spliceosome, Maria De Lourdes Coelho Ribeiro, Julio Espinosa, Sameen Islam, Osvaldo Martinez, Jayesh Jamnadas Thanki, Stephanie Mazariegos, Tam Nguyen, Maya Larina, Bin Xue, Vladimir N. Uversky Jan 2013

Malleable Ribonucleoprotein Machine: Protein Intrinsic Disorder In The Saccharomyces Cerevisiae Spliceosome, Maria De Lourdes Coelho Ribeiro, Julio Espinosa, Sameen Islam, Osvaldo Martinez, Jayesh Jamnadas Thanki, Stephanie Mazariegos, Tam Nguyen, Maya Larina, Bin Xue, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Recent studies revealed that a significant fraction of any given proteome is presented by proteins that do not have unique 3D structures as a whole or in significant parts. These intrinsically disordered proteins possess dramatic structural and functional variability, being especially enriched in signaling and regulatory functions since their lack of fixed structure defines their ability to be involved in interaction with several proteins and allows them to be re-used in multiple pathways. Among recognized disorder-based protein functions are interactions with nucleic acids and multi-target binding; i.e., the functions ascribed to many spliceosomal proteins. Therefore, the spliceosome, a multimegadalton ribonucleoprotein …