On the role of anionic lipids in charged protein interactions with membranes

Eukaryotic cells contain small, highly abundant, nuclear-localized non-coding RNAs [snRNAs (small nuclear RNAs)] which play important roles in splicing of introns from primary genomic transcripts. Through a combination of RNA–RNA and RNA–protein interactions, two of the snRNPs, U1 and U2, recognize the splice sites and the branch site of introns. A complex remodelling of RNA–RNA and protein-based interactions follows, resulting in the assembly of catalytically competent spliceosomes, in which the snRNAs and their bound proteins play central roles. This process involves formation of extensive base-pairing interactions between U2 and U6, U6 and the 5′ splice site, and U5 and the exonic sequences immediately adjacent to the 5′ and 3′ splice sites. Thus RNA–RNA interactions involving U2, U5 and U6 help position the reacting groups of the first and second steps of splicing. In addition, U6 is also thought to participate in formation of the spliceosomal active site. Furthermore, emerging evidence suggests additional roles for snRNAs in regulation of various aspects of RNA biogenesis, from transcription to polyadenylation and RNA stability. These snRNP-mediated regulatory roles probably serve to ensure the co-ordination of the different processes involved in biogenesis of RNAs and point to the central importance of snRNAs in eukaryotic gene expression.

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Faculty Opinions recommendation of Role of cholesterol and polyunsaturated chains in lipid-protein interactions: molecular dynamics simulation of rhodopsin in a realistic membrane environment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1025182.297783 ◽

2005 ◽

Author(s):

Tetsuji Okada

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Protein Interactions ◽

Dynamics Simulation ◽

Lipid Protein Interactions

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Faculty Opinions recommendation of Structure of pulmonary surfactant membranes and films: the role of proteins and lipid-protein interactions.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1123459.580634 ◽

2008 ◽

Author(s):

Matthias Ochs

Keyword(s):

Protein Interactions ◽

Pulmonary Surfactant ◽

Lipid Protein Interactions

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Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

Current Issues in Molecular Biology ◽

10.3390/cimb43020056 ◽

2021 ◽

Vol 43 (2) ◽

pp. 767-781

Author(s):

Vanessa Pinatto Gaspar ◽

Anelise Cardoso Ramos ◽

Philippe Cloutier ◽

José Renato Pattaro Junior ◽

Francisco Ferreira Duarte Junior ◽

...

Keyword(s):

Dna Replication ◽

Protein Interactions ◽

Ribosome Biogenesis ◽

Cell Metabolism ◽

Cell Types ◽

Protein Protein Interactions ◽

Cellular Mechanisms ◽

Cancerous Cell ◽

First Time

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.

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A Global Review on Short Peptides: Frontiers and Perspectives

Molecules ◽

10.3390/molecules26020430 ◽

2021 ◽

Vol 26 (2) ◽

pp. 430

Author(s):

Vasso Apostolopoulos ◽

Joanna Bojarska ◽

Tsun-Thai Chai ◽

Sherif Elnagdy ◽

Krzysztof Kaczmarek ◽

...

Keyword(s):

Protein Interactions ◽

Targeted Delivery ◽

Swot Analysis ◽

Functional Materials ◽

Great Promise ◽

Short Peptides ◽

Altered Peptide Ligands ◽

Short Peptide ◽

Domains Of Life

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide “drugs” initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

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Unlike its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival

Cells ◽

10.3390/cells10010192 ◽

2021 ◽

Vol 10 (1) ◽

pp. 192

Author(s):

Siska Van Belle ◽

Sara El Ashkar ◽

Kateřina Čermáková ◽

Filip Matthijssens ◽

Steven Goossens ◽

...

Keyword(s):

Growth Factor ◽

Cell Survival ◽

Cell Lines ◽

Protein Interactions ◽

Leukemic Cell ◽

Related Protein ◽

Histone Tails ◽

Knockout Mouse Model ◽

Leukemic Cell Lines

HDGF-related protein 2 (HRP-2) is a member of the Hepatoma-Derived Growth Factor-related protein family that harbors the structured PWWP and Integrase Binding Domain, known to associate with methylated histone tails or cellular and viral proteins, respectively. Interestingly, HRP-2 is a paralog of Lens Epithelium Derived Growth Factor p75 (LEDGF/p75), which is essential for MLL-rearranged (MLL-r) leukemia but dispensable for hematopoiesis. Sequel to these findings, we investigated the role of HRP-2 in hematopoiesis and MLL-r leukemia. Protein interactions were investigated by co-immunoprecipitation and validated using recombinant proteins in NMR. A systemic knockout mouse model was used to study normal hematopoiesis and MLL-ENL transformation upon the different HRP-2 genotypes. The role of HRP-2 in MLL-r and other leukemic, human cell lines was evaluated by lentiviral-mediated miRNA targeting HRP-2. We demonstrate that MLL and HRP-2 interact through a conserved interface, although this interaction proved less dependent on menin than the MLL-LEDGF/p75 interaction. The systemic HRP-2 knockout mice only revealed an increase in neutrophils in the peripheral blood, whereas the depletion of HRP-2 in leukemic cell lines and transformed primary murine cells resulted in reduced colony formation independently of MLL-rearrangements. In contrast, primary murine HRP-2 knockout cells were efficiently transformed by the MLL-ENL fusion, indicating that HRP-2, unlike LEDGF/p75, is dispensable for the transformation of MLL-ENL leukemogenesis but important for leukemic cell survival.

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The important role of non‐covalent drug‐protein interactions in drug hypersensitivity reactions

Allergy ◽

10.1111/all.14962 ◽

2021 ◽

Author(s):

Werner J Pichler

Keyword(s):

Protein Interactions ◽

Drug Hypersensitivity ◽

Hypersensitivity Reactions ◽

Drug Hypersensitivity Reactions

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Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update

Current Medicinal Chemistry ◽

10.2174/0929867324666170426095015 ◽

2018 ◽

Vol 25 (1) ◽

pp. 5-21 ◽

Cited By ~ 25

Author(s):

Ylenia Cau ◽

Daniela Valensin ◽

Mattia Mori ◽

Sara Draghi ◽

Maurizio Botta

Keyword(s):

Protein Interactions ◽

Molecular Mechanisms ◽

Physiological Role ◽

Specific Protein ◽

Protein Protein Interactions ◽

Cellular Processes ◽

Protein Partners ◽

High Sequence Homology ◽

Small Molecule Modulators

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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