Withdrawal notice to ‘WITHDRAWN: Specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1B and a poly-ARG interferon beta-1B analogue’ [International Journal of Pharmaceutics 589 (2020) 119913]

14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.

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Metallocluster transactions: dynamic protein interactions guide the biosynthesis of Fe–S clusters in bacteria

Biochemical Society Transactions ◽

10.1042/bst20180365 ◽

2018 ◽

Vol 46 (6) ◽

pp. 1593-1603 ◽

Cited By ~ 9

Author(s):

Chenkang Zheng ◽

Patricia C. Dos Santos

Keyword(s):

Protein Interactions ◽

Protein Complexes ◽

Specific Protein ◽

Biological Synthesis ◽

Cluster Assembly ◽

Sequence Motifs ◽

Protein Protein Interactions ◽

Cysteine Desulfurase ◽

Wide Range ◽

Domains Of Life

Iron–sulfur (Fe–S) clusters are ubiquitous cofactors present in all domains of life. The chemistries catalyzed by these inorganic cofactors are diverse and their associated enzymes are involved in many cellular processes. Despite the wide range of structures reported for Fe–S clusters inserted into proteins, the biological synthesis of all Fe–S clusters starts with the assembly of simple units of 2Fe–2S and 4Fe–4S clusters. Several systems have been associated with the formation of Fe–S clusters in bacteria with varying phylogenetic origins and number of biosynthetic and regulatory components. All systems, however, construct Fe–S clusters through a similar biosynthetic scheme involving three main steps: (1) sulfur activation by a cysteine desulfurase, (2) cluster assembly by a scaffold protein, and (3) guided delivery of Fe–S units to either final acceptors or biosynthetic enzymes involved in the formation of complex metalloclusters. Another unifying feature on the biological formation of Fe–S clusters in bacteria is that these systems are tightly regulated by a network of protein interactions. Thus, the formation of transient protein complexes among biosynthetic components allows for the direct transfer of reactive sulfur and Fe–S intermediates preventing oxygen damage and reactions with non-physiological targets. Recent studies revealed the importance of reciprocal signature sequence motifs that enable specific protein–protein interactions and consequently guide the transactions between physiological donors and acceptors. Such findings provide insights into strategies used by bacteria to regulate the flow of reactive intermediates and provide protein barcodes to uncover yet-unidentified cellular components involved in Fe–S metabolism.

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Bi-directional protein-protein interactions control liquid-liquid phase separation of PSD-95 and its interaction partners

10.1101/2021.03.03.433781 ◽

2021 ◽

Author(s):

Nikolaj Riis Christensen ◽

Christian Parsbæk Pedersen ◽

Vita Sereikaite ◽

Jannik Nedergaard Pedersen ◽

Maria Vistrup-Parry ◽

...

Keyword(s):

Phase Separation ◽

Liquid Phase ◽

Protein Interactions ◽

Postsynaptic Density ◽

Specific Protein ◽

Liquid Phase Separation ◽

Protein Protein Interactions ◽

New Perspective ◽

Liquid Liquid Phase Separation

SUMMARYThe organization of the postsynaptic density (PSD), a protein-dense semi-membraneless organelle, is mediated by numerous specific protein-protein interactions (PPIs) which constitute a functional post-synapse. Postsynaptic density protein 95 (PSD-95) interacts with a manifold of proteins, including the C-terminal of transmembrane AMPA receptor (AMAPR) regulatory proteins (TARPs). Here, we uncover the minimal essential peptide responsible for the stargazin (TARP-γ2) mediated liquid-liquid phase separation (LLPS) formation of PSD-95 and other key protein constituents of the PSD. Furthermore, we find that pharmacological inhibitors of PSD-95 can facilitate formation of LLPS. We found that in some cases LLPS formation is dependent on multivalent interactions while in other cases short peptides carrying a high charge are sufficient to promote LLPS in complex systems. This study offers a new perspective on PSD-95 interactions and their role in LLPS formation, while also considering the role of affinity over multivalency in LLPS systems.

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Coevolution-based prediction of protein–protein interactions in polyketide biosynthetic assembly lines

Bioinformatics ◽

10.1093/bioinformatics/btaa595 ◽

2020 ◽

Vol 36 (19) ◽

pp. 4846-4853 ◽

Cited By ~ 1

Author(s):

Yan Wang ◽

Miguel Correa Marrero ◽

Marnix H Medema ◽

Aalt D J van Dijk

Keyword(s):

Protein Interactions ◽

Antitumor Agents ◽

Acyl Carrier Protein ◽

Specific Protein ◽

Combinatorial Biosynthesis ◽

Supplementary Information ◽

Protein Protein Interactions ◽

Assembly Lines ◽

Specific Order ◽

Encoding Genes

Abstract Motivation Polyketide synthases (PKSs) are enzymes that generate diverse molecules of great pharmaceutical importance, including a range of clinically used antimicrobials and antitumor agents. Many polyketides are synthesized by cis-AT modular PKSs, which are organized in assembly lines, in which multiple enzymes line up in a specific order. This order is defined by specific protein–protein interactions (PPIs). The unique modular structure and catalyzing mechanism of these assembly lines makes their products predictable and also spurred combinatorial biosynthesis studies to produce novel polyketides using synthetic biology. However, predicting the interactions of PKSs, and thereby inferring the order of their assembly line, is still challenging, especially for cases in which this order is not reflected by the ordering of the PKS-encoding genes in the genome. Results Here, we introduce PKSpop, which uses a coevolution-based PPI algorithm to infer protein order in PKS assembly lines. Our method accurately predicts protein orders (93% accuracy). Additionally, we identify new residue pairs that are key in determining interaction specificity, and show that coevolution of N- and C-terminal docking domains of PKSs is significantly more predictive for PPIs than coevolution between ketosynthase and acyl carrier protein domains. Availability and implementation The code is available on http://www.bif.wur.nl/ (under ‘Software’). Supplementary information Supplementary data are available at Bioinformatics online.

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The study of protein–protein interactions in bacteria

Canadian Journal of Microbiology ◽

10.1139/w2012-104 ◽

2012 ◽

Vol 58 (11) ◽

pp. 1241-1257 ◽

Cited By ~ 8

Author(s):

Roberto Velasco-García ◽

Rocío Vargas-Martínez

Keyword(s):

Hybrid System ◽

High Throughput ◽

Protein Interactions ◽

Specific Protein ◽

False Positives ◽

Interaction Networks ◽

Protein Protein Interactions ◽

Extensive Data ◽

False Positives And Negatives

Many of the functions fulfilled by proteins in the cell require specific protein–protein interactions (PPI). During the last decade, the use of high-throughput experimental technologies, primarily based on the yeast 2-hybrid system, generated extensive data currently located in public databases. This information has been used to build interaction networks for different species. Unfortunately, due to the nature of the yeast 2-hybrid system, these databases contain many false positives and negatives, thus they require purging. A method for confirming these PPI is to test them using a technique that operates in vivo and detects binary PPI. This article comprises an overview of the study of PPI and describes the main techniques that have been used to identify bacterial PPI, prioritizing those that can be used for their verification, and it also mentions a number of PPI that have been identified or confirmed using these methods.

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