48,786 results match your criteria protein-interaction domains

Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials.

ACS Appl Mater Interfaces 2021 Jun 15. Epub 2021 Jun 15.

Laboratory for Environmental and Life Sciences, University of Nova Gorica Nova Gorica 5000, Slovenia.

Nanobodies represent valuable tools in advanced therapeutic strategies but their small size (∼2.5 × ∼ 4 nm) and limited valence for interactions might pose restrictions for applications, especially regarding their modest capacity for multivalent and cooperative interaction. In this work, modular protein constructs have been designed, in which nanobodies are fused to protein domains to provide further functionalities and to favor oligomerization into stable self-assembled nanoparticles. Read More

View Article and Full-Text PDF

The Nuclear Pore Complex as a Transcription Regulator.

Cold Spring Harb Perspect Biol 2021 Jun 14. Epub 2021 Jun 14.

Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA.

The nuclear pore complex (NPC) is a highly conserved channel in the nuclear envelope that mediates mRNA export to the cytosol and bidirectional protein transport. Many chromosomal loci physically interact with nuclear pore proteins (Nups), and interactions with Nups can promote transcriptional repression, transcriptional activation, and transcriptional poising. Interaction with the NPC also affects the spatial arrangement of genes, interchromosomal clustering, and folding of topologically associated domains. Read More

View Article and Full-Text PDF

Inhibition of K-Ras4B-plasma membrane association with a membrane microdomain-targeting peptide.

Chem Sci 2019 Dec 3;11(3):826-832. Epub 2019 Dec 3.

Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University Beijing 100084 China

The association of K-Ras4B protein with plasma membrane (PM) is required for its signaling activity. Thus, direct inhibition of K-Ras4B-PM interaction could be a potential anti-Ras therapeutic strategy. However, it remains challenging to modulate such protein-PM interaction. Read More

View Article and Full-Text PDF
December 2019

Kinetics of CagA type IV secretion by Helicobacter pylori and the requirement for substrate unfolding.

Mol Microbiol 2021 Jun 14. Epub 2021 Jun 14.

Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Medical Faculty, LMU Munich, Munich, Germany.

Type IV secretion of effector proteins is an important principle for interaction of human pathogens with their target cells. The corresponding secretion systems may transport a multitude of effector proteins that have to be deployed in the respective spatiotemporal context, or only a single translocated protein, as in the case of the CagA effector protein produced by the human gastric pathogen Helicobacter pylori. For a more detailed analysis of the kinetics and mode of action of CagA type IV secretion by H. Read More

View Article and Full-Text PDF

Talin mechanosensitivity is modulated by a direct interaction with cyclin-dependent kinase-1.

J Biol Chem 2021 Jun 9:100837. Epub 2021 Jun 9.

School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK. Electronic address:

Talin (TLN1) is a mechanosensitive component of adhesion complexes that directly couples integrins to the actin cytoskeleton. In response to force, talin undergoes switch-like behavior of its multiple rod domains that modulate interactions with its binding partners. Cyclin-dependent kinase-1 (CDK1) is a key regulator of the cell cycle, exerting its effects through synchronized phosphorylation of a large number of protein targets. Read More

View Article and Full-Text PDF

High resolution crystal structure of the Borreliella burgdorferi PlzA protein in complex with c-di-GMP: new insights into the interaction of c-di-GMP with the novel xPilZ domain.

Pathog Dis 2021 Jun 12. Epub 2021 Jun 12.

Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, 1112 East Clay Street, Room 101 McGuire Hall, Richmond, VA 23298-0678 USA.

In the tick-borne pathogens, Borreliella burgdorferi and Borrelia hermsii, c-di-GMP is produced by a single diguanylate cyclase (Rrp1). In these pathogens, the Plz proteins (PlzA, B and C) are the only c-di-GMP receptors identified to date and PlzA is the sole c-di-GMP receptor found in all Borreliella isolates. Bioinformatic analyses suggest that PlzA has a unique PilZN3-PilZ architecture with the relatively uncommon xPilZ domain. Read More

View Article and Full-Text PDF

The PHY domain dimer interface of bacteriophytochromes mediates cross-talk between photosensory modules and output domains.

J Mol Biol 2021 Jun 8:167092. Epub 2021 Jun 8.

Institute of Biochemistry, Graz University of Technology, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria. Electronic address:

Protein dynamics play a major role for the catalytic function of enzymes, the interaction of protein complexes or signal integration in regulatory proteins. In the context of multi-domain proteins involved in light-regulation of enzymatic effectors, the central role of conformational dynamics is well established. Light activation of sensory modules is followed by long-range signal transduction to different effectors; rather than domino-style structural rearrangements, a complex interplay of functional elements is required to maintain functionality. Read More

View Article and Full-Text PDF

DMA-tudor interaction modules control the specificity of in vivo condensates.

Cell 2021 Jun 4. Epub 2021 Jun 4.

Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Cell Biology, Yale University, New Haven, CT 06520, USA. Electronic address:

Biomolecular condensation is a widespread mechanism of cellular compartmentalization. Because the "survival of motor neuron protein" (SMN) is implicated in the formation of three different membraneless organelles (MLOs), we hypothesized that SMN promotes condensation. Unexpectedly, we found that SMN's globular tudor domain was sufficient for dimerization-induced condensation in vivo, whereas its two intrinsically disordered regions (IDRs) were not. Read More

View Article and Full-Text PDF

Protein-Protein Interactions Shape Genomic Autoimmunity in the Adaptively-Evolving Rhino-Deadlock-Cutoff (RDC) Complex.

Erin S Kelleher

Genome Biol Evol 2021 Jun 11. Epub 2021 Jun 11.

University of Houston, Houston, TX 77025, USA.

The piRNA pathway is a genomic defense system that controls the movement of transposable elements (TEs) through transcriptional and post-transcriptional silencing. While TE defense is critical to ensuring germline genome integrity, it is equally critical that the piRNA pathway avoids autoimmunity in the form of silencing host genes. Ongoing cycles of selection for expanded control of invading TEs, followed by selection for increased specificity to reduce impacts on host genes, are proposed to explain the frequent signatures of adaptive evolution among piRNA pathway proteins. Read More

View Article and Full-Text PDF

Mechanistic insights into TNFR1/MADD death domains in Alzheimer's disease through conformational molecular dynamic analysis.

Sci Rep 2021 Jun 10;11(1):12256. Epub 2021 Jun 10.

Department of Human Anatomy and Physiology, the Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa.

Proteins are tiny players involved in the activation and deactivation of multiple signaling cascades through interactions in cells. The TNFR1 and MADD interact with each other and mediate downstream protein signaling pathways which cause neuronal cell death and Alzheimer's disease. In the current study, a molecular docking approach was employed to explore the interactive behavior of TNFR1 and MADD proteins and their role in the activation of downstream signaling pathways. Read More

View Article and Full-Text PDF

Transcriptomic and functional proteomics analyses to unveil the common and unique pathway(s) of neuritogenesis induced by Russell's viper venom nerve growth factor in rat pheochromocytoma neuronal cells.

Expert Rev Proteomics 2021 Jun 10. Epub 2021 Jun 10.

Department of Molecular Biology and Biotechnology, School of Sciences, Tezpur University, Tezpur 784028, Assam, India.

: The snake venom nerve growth factor (NGF)-induced signal transduction mechanism has never been explored.: Homology modeling and molecular dynamic studies of the interaction between Russell's viper venom NGF (RVV-NGFa) and mammalian tropomyosin-receptor kinase A (TrkA) was done by computational analysis. Transcriptomic and quantitative tandem mass spectrometry analyses determined the expression of intracellular genes and proteins, respectively, in RVV-NGFa-treated PC-12 neuronal cells. Read More

View Article and Full-Text PDF

RHBDD2‑WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells.

Oncol Rep 2021 Aug 10;46(2). Epub 2021 Jun 10.

Basic and Applied Immunological Research Center, School of Medical Sciences, National University of La Plata, La Plata, Buenos Aires CP1900, Argentina.

Rhomboid pseudoproteases are catalytically inactive members of the rhomboid superfamily that modulate the traffic, turnover and activity of their target proteins. Rhomboid domain containing 2 () is a rhomboid family member overexpressed during mammary gland development and advanced stages of breast cancer. Interactome profiling studies have identified RHBDD2 as a novel binding partner of WW domain‑containing oxidoreductase (WWOX) protein. Read More

View Article and Full-Text PDF

SMCHD1's ubiquitin-like domain is required for N-terminal dimerization and chromatin localization.

Biochem J 2021 Jun 10. Epub 2021 Jun 10.

Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

Structural Maintenance of Chromosomes flexible Hinge Domain-containing 1 (SMCHD1) is an epigenetic regulator that mediates gene expression silencing at targeted sites across the genome. Our current understanding of SMCHD1's molecular mechanism, and how substitutions within SMCHD1 lead to the diseases, facioscapulohumeral muscular dystrophy (FSHD) and Bosma arhinia microphthalmia syndrome (BAMS), are only emerging. Recent structural studies of its two component domains - the N-terminal ATPase and C-terminal SMC hinge - suggest that dimerization of each domain plays a central role in SMCHD1 function. Read More

View Article and Full-Text PDF

Thermodynamic consequences of Tyr to Trp mutations in the cation-π-mediated binding of trimethyllysine by the HP1 chromodomain.

Chem Sci 2020 Mar 4;11(13):3495-3500. Epub 2020 Mar 4.

University of North Carolina at Chapel Hill 131 South Road, Campus Box 3290 Chapel Hill NC 27599 USA

Evolution has converged on cation-π interactions for recognition of quaternary alkyl ammonium groups such as trimethyllysine (Kme3). While computational modelling indicates that Trp provides the strongest cation-π interaction of the native aromatic amino acids, there is limited corroborative data from measurements within proteins. Herein we investigate a Tyr to Trp mutation in the binding pocket of the HP1 chromodomain, a reader protein that recognizes Kme3. Read More

View Article and Full-Text PDF

HIV-1 Gag recruits oligomeric Vpr via two binding sites in p6, but both mature p6 and Vpr are rapidly lost upon target cell entry.

J Virol 2021 Jun 9:JVI0055421. Epub 2021 Jun 9.

Retroviral Replication Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom.

The p12 region of MLV Gag and the p6 region of HIV-1 Gag contain late-domains required for virus budding. Additionally, the accessory protein Vpr is recruited into HIV particles via p6. Mature p12 is essential for early viral replication events, but the role of mature p6 in early replication is unknown. Read More

View Article and Full-Text PDF

The zinc-finger protein Red1 orchestrates MTREC submodules and binds the Mtl1 helicase arch domain.

Nat Commun 2021 06 8;12(1):3456. Epub 2021 Jun 8.

Heidelberg University Biochemistry Center (BZH), Heidelberg, Germany.

Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome in a process requiring the RNA helicase Mtr4 and specific adaptor complexes for RNA substrate recognition. The PAXT and MTREC complexes have recently been identified as homologous exosome adaptors in human and fission yeast, respectively. The eleven-subunit MTREC comprises the zinc-finger protein Red1 and the Mtr4 homologue Mtl1. Read More

View Article and Full-Text PDF

Functional Structure in Production Networks.

Front Big Data 2021 21;4:666712. Epub 2021 May 21.

Computational Science Lab, Faculty of Science, University of Amsterdam, Amsterdam, Netherlands.

Production networks are integral to economic dynamics, yet dis-aggregated network data on inter-firm trade is rarely collected and often proprietary. Here we situate company-level production networks within a wider space of networks that are different in nature, but similar in local connectivity structure. Through this lens, we study a regional and a national network of inferred trade relationships reconstructed from Dutch national economic statistics and re-interpret prior empirical findings. Read More

View Article and Full-Text PDF

Understanding How Staphylococcal Autolysin Domains Interact With Polystyrene Surfaces.

Front Microbiol 2021 19;12:658373. Epub 2021 May 19.

Department of Chemistry, Mississippi State University, Mississippi State, MS, United States.

Biofilms, when formed on medical devices, can cause malfunctions and reduce the efficiency of these devices, thus complicating treatments and serving as a source of infection. The autolysin protein of contributes to its biofilm forming ability, especially on polystyrene surfaces. R2ab and amidase are autolysin protein domains thought to have high affinity to polystyrene surfaces, and they are involved in initial bacterial attachment in biofilm formation. Read More

View Article and Full-Text PDF

ARL15 modulates magnesium homeostasis through N-glycosylation of CNNMs.

Cell Mol Life Sci 2021 Jun 5. Epub 2021 Jun 5.

Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands.

Cyclin M (CNNM1-4) proteins maintain cellular and body magnesium (Mg) homeostasis. Using various biochemical approaches, we have identified members of the CNNM family as direct interacting partners of ADP-ribosylation factor-like GTPase 15 (ARL15), a small GTP-binding protein. ARL15 interacts with CNNMs at their carboxyl-terminal conserved cystathionine-β-synthase (CBS) domains. Read More

View Article and Full-Text PDF

SepF is the FtsZ anchor in archaea, with features of an ancestral cell division system.

Nat Commun 2021 06 4;12(1):3214. Epub 2021 Jun 4.

Evolutionary Biology of the Microbial Cell Unit, CNRS UMR2001, Department of Microbiology, Institut Pasteur, Paris, France.

Most archaea divide by binary fission using an FtsZ-based system similar to that of bacteria, but they lack many of the divisome components described in model bacterial organisms. Notably, among the multiple factors that tether FtsZ to the membrane during bacterial cell constriction, archaea only possess SepF-like homologs. Here, we combine structural, cellular, and evolutionary analyses to demonstrate that SepF is the FtsZ anchor in the human-associated archaeon Methanobrevibacter smithii. Read More

View Article and Full-Text PDF

Identification of RNA-Binding Proteins Associated to RNA Structural Elements.

Methods Mol Biol 2021 ;2323:109-119

Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.

RNA motifs guide the interaction with specific proteins leading to the assembly of ribonucleoprotein complexes that perform key functions in cellular processes. Internal ribosome entry site (IRES) elements are organized in structural domains that determine internal initiation of translation. In this chapter we describe a pull-down assay using streptavidin-aptamer tagged RNAs that combines RNA structure-dependent protein isolation with proteomic analysis to identify novel interactors recognizing RNA structural domains. Read More

View Article and Full-Text PDF
January 2021

Circ-ACAP2 facilitates the progression of colorectal cancer through mediating miR-143-3p/FZD4 axis.

Eur J Clin Invest 2021 Jun 4:e13607. Epub 2021 Jun 4.

Department of Oncology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, P.R. China.

Background: Circular RNAs (circRNAs) play crucial roles in multiple cancers, including colorectal cancer (CRC). Here, we explored the role of circRNA ArfGAP with coiled-coil, ankyrin repeat and PH domains 2 (circ-ACAP2) in the progression and radioresistance of CRC.

Methods: Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were used to detect RNA and protein expression, respectively. Read More

View Article and Full-Text PDF

Evolution of KIPPIS as a versatile platform for evaluating intracellularly functional peptide aptamers.

Sci Rep 2021 Jun 3;11(1):11758. Epub 2021 Jun 3.

Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Chimeric proteins have been widely used to evaluate intracellular protein-protein interactions (PPIs) in living cells with various readouts. By combining an interleukin-3-dependent murine cells and chimeric proteins containing a receptor tyrosine kinase c-kit, we previously established a c-kit-based PPI screening (KIPPIS) system to evaluate and select protein binders. In the KIPPIS components, proteins of interest are connected with a chemically inducible helper module and the intracellular domain of the growth-signaling receptor c-kit, which detects PPIs based on cell proliferation as a readout. Read More

View Article and Full-Text PDF

Function and molecular mechanisms of APE2 in genome and epigenome integrity.

Mutat Res 2021 Jan-Jun;787:108347. Epub 2020 Nov 16.

Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, 28223, United States. Electronic address:

APE2 is a rising vital player in the maintenance of genome and epigenome integrity. In the past several years, a series of studies have shown the critical roles and functions of APE2. We seek to provide the first comprehensive review on several aspects of APE2 in genome and epigenome integrity. Read More

View Article and Full-Text PDF
November 2020

A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2'-O methylation of its first nucleotide.

Nat Commun 2021 06 2;12(1):3287. Epub 2021 Jun 2.

Greehey Children's Cancer Research Institute, University of Texas Health at San Antonio, San Antonio, TX, USA.

The SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2'-OH of the first transcribed nucleotide of the viral mRNA by covalently attaching a methyl group to it. The 2'-O methylation of the first nucleotide converts the status of mRNA cap from Cap-0 to Cap-1, and thus, helps the virus evade immune surveillance in host cells. Here, we report two structures of nsp16/nsp10 representing pre- and post-release states of the RNA product (Cap-1). Read More

View Article and Full-Text PDF

Through bonds or contacts? Mapping protein vibrational energy transfer using non-canonical amino acids.

Nat Commun 2021 06 2;12(1):3284. Epub 2021 Jun 2.

Institute of Biophysics, Goethe University Frankfurt, Frankfurt/Main, Germany.

Vibrational energy transfer (VET) is essential for protein function. It is responsible for efficient energy dissipation in reaction sites, and has been linked to pathways of allosteric communication. While it is understood that VET occurs via backbone as well as via non-covalent contacts, little is known about the competition of these two transport channels, which determines the VET pathways. Read More

View Article and Full-Text PDF

Structure of the merozoite surface protein 1 from .

Sci Adv 2021 Jun 2;7(23). Epub 2021 Jun 2.

Max-Planck-Institute of Biophysics, Frankfurt am Main, Germany.

The merozoite surface protein 1 (MSP-1) is the most abundant protein on the surface of the erythrocyte-invading merozoite, the causative agent of malaria. MSP-1 is essential for merozoite formation, entry into and escape from erythrocytes, and is a promising vaccine candidate. Here, we present monomeric and dimeric structures of full-length MSP-1. Read More

View Article and Full-Text PDF

PSMD9 ribosomal protein network maintains nucleolar architecture and WT p53 levels.

Biochem Biophys Res Commun 2021 Jul 30;563:105-112. Epub 2021 May 30.

Protein Interactome Lab for Structural and Functional Biology, Advanced Centre for Treatment, Research and Education in Cancer, Sector 22, Kharghar, Navi Mumbai, Maharashtra, 410210, India; Homi Bhabha National Institute, BARC Training School Complex, Anushaktinagar, Mumbai, Maharashtra, 400094, India. Electronic address:

Capitalizing on an unexpected observation that multiple free ribosomal proteins co-purify/pull-down with PSMD9, we report here for the first time that PSMD9 is necessary to maintain the morphology and integrity of the nucleolus. As seen by NPM1 immunofluorescence and electron microscopy, the nucleolar structure is clearly disrupted in PSMD9 null MCF7 breast cancer cells. The resultant stress is pronounced leading to the accumulation of WT p53 and slow growth. Read More

View Article and Full-Text PDF

NAP1L1 and NAP1L4 binding to Hypervariable Domain of Chikungunya Virus nsP3 Protein is bivalent and requires phosphorylation.

J Virol 2021 Jun 2:JVI0083621. Epub 2021 Jun 2.

Department of Microbiology, University of Alabama at Birmingham, AL, USA.

Chikungunya virus (CHIKV) is one of the most pathogenic members of the genus in the family. Within the last two decades, CHIKV has expanded its presence to both hemispheres and is currently circulating in both Old and New Worlds. Despite the severity and persistence of the arthritis it causes in humans, no approved vaccines or therapeutic means have been developed for CHIKV infection. Read More

View Article and Full-Text PDF