scholarly journals Structural basis for protein-protein interactions in the 14-3-3 protein family

2006 ◽  
Vol 103 (46) ◽  
pp. 17237-17242 ◽  
Author(s):  
X. Yang ◽  
W. H. Lee ◽  
F. Sobott ◽  
E. Papagrigoriou ◽  
C. V. Robinson ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Family ◽  
Structural Basis ◽  
Protein Protein Interactions

scholarly journals Characterization of COMMD protein–protein interactions in NF-κB signalling

2006 ◽  
Vol 398 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Prim de Bie ◽  
Bart van de Sluis ◽  
Ezra Burstein ◽  
Karen J. Duran ◽  
Ruud Berger ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Copper Metabolism ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Protein Family ◽  
Amino Acid Residues ◽  
Protein Protein Interactions ◽  
Necrosis Factor

COMMD [copper metabolism gene MURR1 (mouse U2af1-rs1 region 1) domain] proteins constitute a recently identified family of NF-κB (nuclear factor κB)-inhibiting proteins, characterized by the presence of the COMM domain. In the present paper, we report detailed investigation of the role of this protein family, and specifically the role of the COMM domain, in NF-κB signalling through characterization of protein–protein interactions involving COMMD proteins. The small ubiquitously expressed COMMD6 consists primarily of the COMM domain. Therefore COMMD1 and COMMD6 were analysed further as prototype members of the COMMD protein family. Using specific antisera, interaction between endogenous COMMD1 and COMMD6 is described. This interaction was verified by independent techniques, appeared to be direct and could be detected throughout the whole cell, including the nucleus. Both proteins inhibit TNF (tumour necrosis factor)-induced NF-κB activation in a non-synergistic manner. Mutation of the amino acid residues Trp24 and Pro41 in the COMM domain of COMMD6 completely abolished the inhibitory effect of COMMD6 on TNF-induced NF-κB activation, but this was not accompanied by loss of interaction with COMMD1, COMMD6 or the NF-κB subunit RelA. In contrast with COMMD1, COMMD6 does not bind to IκBα (inhibitory κBα), indicating that both proteins inhibit NF-κB in an overlapping, but not completely similar, manner. Taken together, these data support the significance of COMMD protein–protein interactions and provide new mechanistic insight into the function of this protein family in NF-κB signalling.

Uracil recognition by archaeal family B DNA polymerases

2003 ◽  
Vol 31 (3) ◽  
pp. 699-702 ◽  
Author(s):  
B.A. Connolly ◽  
M.J. Fogg ◽  
G. Shuttleworth ◽  
B.T. Wilson
Keyword(s):  
Dna Synthesis ◽  
Protein Interactions ◽  
Replication Fork ◽  
Dna Polymerases ◽  
Structural Basis ◽  
Dna Glycosylases ◽  
Protein Protein Interactions ◽  
Sensing Mechanism ◽  
Uridine Triphosphate

Archaeal family-B DNA polymerases possess a novel uracil-sensing mechanism. A specialized pocket scans the template, ahead of the replication fork, for the presence of uracil; on encountering this base, DNA synthesis is stalled. The structural basis for uracil recognition by polymerases is described and compared with other uracil-recognizing enzymes (uridine-triphosphate pyrophophatases and uracil-DNA glycosylases). Remarkably, protein–protein interactions between all three archaeal uracil sensors are observed; possibly the enzymes co-operate to efficiently eliminate uracil from archaeal genomes.

scholarly journals Novel Topology of BfpE, a Cytoplasmic Membrane Protein Required for Type IV Fimbrial Biogenesis in EnteropathogenicEscherichia coli

2001 ◽  
Vol 183 (15) ◽  
pp. 4435-4450 ◽  
Author(s):  
T. Eric Blank ◽  
Michael S. Donnenberg
Keyword(s):  
Alkaline Phosphatase ◽  
Membrane Protein ◽  
Protein Interactions ◽  
Cytoplasmic Membrane ◽  
Membrane Topology ◽  
Structural Basis ◽  
Protein Protein Interactions ◽  
Type Iv ◽  
C Terminus ◽  
Gradient Fractionation

ABSTRACT Enteropathogenic Escherichia coli (EPEC) produces the bundle-forming pilus (BFP), a type IV fimbria that has been implicated in virulence, autoaggregation, and localized adherence to epithelial cells. The bfpE gene is one of a cluster of bfpgenes previously shown to encode functions that direct BFP biosynthesis. Here, we show that an EPEC strain carrying a nonpolar mutation in bfpE fails to autoaggregate, adhere to HEp-2 cells, or form BFP, thereby demonstrating that BfpE is required for BFP biogenesis. BfpE is a cytoplasmic membrane protein of the GspF family. To determine the membrane topology of BfpE, we fused bfpEderivatives containing 3′ truncations and/or internal deletions to alkaline phosphatase and/or β-galactosidase reporter genes, whose products are active only when localized to the periplasm or cytoplasm, respectively. In addition, we constructed BfpE sandwich fusions using a dual alkaline phosphatase/β-galactosidase reporter cassette and analyzed BfpE deletion derivatives by sucrose density flotation gradient fractionation. The data from these analyses support a topology in which BfpE contains four hydrophobic transmembrane (TM) segments, a large cytoplasmic segment at its N terminus, and a large periplasmic segment near its C terminus. This topology is dramatically different from that of OutF, another member of the GspF family, which has three TM segments and is predominantly cytoplasmic. These findings provide a structural basis for predicting protein-protein interactions required for assembly of the BFP biogenesis machinery.

scholarly journals UHM–ULM interactions in the RBM39–U2AF65 splicing-factor complex

2016 ◽  
Vol 72 (4) ◽  
pp. 497-511 ◽  
Author(s):  
Galina A. Stepanyuk ◽  
Pedro Serrano ◽  
Eigen Peralta ◽  
Carol L. Farr ◽  
Herbert L. Axelrod ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Rna Binding ◽  
Splicing Factor ◽  
Structural Basis ◽  
Titration Calorimetry ◽  
Protein Protein Interactions ◽  
Rrm Domain ◽  
Nmr Structures ◽  
Binding Interface ◽  
Cell Extracts

RNA-binding protein 39 (RBM39) is a splicing factor and a transcriptional co-activator of estrogen receptors and Jun/AP-1, and its function has been associated with malignant progression in a number of cancers. The C-terminal RRM domain of RBM39 belongs to the U2AF homology motif family (UHM), which mediate protein–protein interactions through a short tryptophan-containing peptide known as the UHM-ligand motif (ULM). Here, crystal and solution NMR structures of the RBM39-UHM domain, and the crystal structure of its complex with U2AF65-ULM, are reported. The RBM39–U2AF65 interaction was confirmed by co-immunoprecipitation from human cell extracts, by isothermal titration calorimetry and by NMR chemical shift perturbation experiments with the purified proteins. When compared with related complexes, such as U2AF35–U2AF65 and RBM39–SF3b155, the RBM39-UHM–U2AF65-ULM complex reveals both common and discriminating recognition elements in the UHM–ULM binding interface, providing a rationale for the known specificity of UHM–ULM interactions. This study therefore establishes a structural basis for specific UHM–ULM interactions by splicing factors such as U2AF35, U2AF65, RBM39 and SF3b155, and a platform for continued studies of intermolecular interactions governing disease-related alternative splicing in eukaryotic cells.

scholarly journals Structural Basis for Fe–S Cluster Assembly and tRNA Thiolation Mediated by IscS Protein–Protein Interactions

PLoS Biology ◽  
2010 ◽  
Vol 8 (4) ◽  
pp. e1000354 ◽  
Author(s):  
Rong Shi ◽  
Ariane Proteau ◽  
Magda Villarroya ◽  
Ismaïl Moukadiri ◽  
Linhua Zhang ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Structural Basis ◽  
Cluster Assembly ◽  
Protein Protein Interactions

scholarly journals Structural basis for the interaction of SARS-CoV-2 virulence factor nsp1 with Pol α - Primase

2021 ◽  
Author(s):  
Mairi L Kilkenny ◽  
Charlotte E Veale ◽  
Amir Guppy ◽  
Steven W Hardwick ◽  
Dimitri Y Chirgadze ◽  
...  
Keyword(s):  
Virulence Factor ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Structural Basis ◽  
Structural Protein ◽  
Protein Protein Interactions ◽  
Major Virulence Factor ◽  
Biochemical Characterisation ◽  
Human Proteins ◽  
Primase Complex

The molecular mechanisms that drive the infection by the SARS-CoV-2 coronavirus, the causative agent of the COVID-19 (Coronavirus disease-2019) pandemic, are under intense current scrutiny, to understand how the virus operates and to uncover ways in which the disease can be prevented or alleviated. Recent cell-based analyses of SARS-CoV-2 protein - protein interactions have mapped the human proteins targeted by the virus. The DNA polymerase α - primase complex or primosome, responsible for initiating DNA synthesis in genomic duplication, was identified as a target of nsp1 (non structural protein 1), a major virulence factor in the SARS-CoV-2 infection. Here, we report the biochemical characterisation of the interaction between nsp1 and the primosome and the cryoEM structure of the primosome - nsp1 complex. Our data provide a structural basis for the reported interaction between the primosome and nsp1. They suggest that Pol α - primase plays a part in the immune response to the viral infection, and that its targeting by SARS-CoV-2 aims to interfere with such function.

scholarly journals Molecular and structural mechanisms of ZZ domain-mediated cargo recognition by autophagy receptor Nbr1

2021 ◽  
Author(s):  
Ying-Ying Wang ◽  
Jianxiu Zhang ◽  
Xiao-Man Liu ◽  
Meng-Qiu Dong ◽  
Keqiong Ye ◽  
...  
Keyword(s):  
High Resolution ◽  
Fission Yeast ◽  
Protein Interactions ◽  
Specific Protein ◽  
Structural Basis ◽  
Protein Protein Interactions ◽  
Selective Autophagy ◽  
Specific Manner ◽  
Autophagy Pathway ◽  
Structural Mechanisms

AbstractIn selective autophagy, cargo selectivity is determined by autophagy receptors. However, it remains scarcely understood how autophagy receptors recognize specific protein cargos. In the fission yeast Schizosaccharomyces pombe, a selective autophagy pathway termed Nbr1-mediated vacuolar targeting (NVT) employs Nbr1, an autophagy receptor conserved across eukaryotes including humans, to target cytosolic hydrolases into the vacuole. Here, we identify two new NVT cargos, the mannosidase Ams1 and the aminopeptidase Ape4, that bind competitively to the first ZZ domain of Nbr1 (Nbr1-ZZ1). High-resolution cryo-EM analyses reveal how a single ZZ domain recognizes two distinct protein cargos. Nbr1-ZZ1 not only recognizes the N-termini of cargos via a conserved acidic pocket, similar to other characterized ZZ domains, but also engages additional parts of cargos in a cargo-specific manner. Our findings unveil a single-domain bispecific mechanism of autophagy cargo recognition, elucidate its underlying structural basis, and expand the understanding of ZZ domain-mediated protein-protein interactions.

scholarly journals Structural Profiling of Bacterial Effectors Reveals Enrichment of Host-Interacting Domains and Motifs

2021 ◽  
Vol 8 ◽  
Author(s):  
Yangchun Frank Chen ◽  
Yu Xia
Keyword(s):  
Protein Interactions ◽  
Effector Proteins ◽  
Host Cells ◽  
Structural Basis ◽  
Protein Protein Interactions ◽  
Specific Domain ◽  
Bacterial Proteins ◽  
Domain Interactions ◽  
Host Signaling ◽  
Bacterial Effectors

Effector proteins are bacterial virulence factors secreted directly into host cells and, through extensive interactions with host proteins, rewire host signaling pathways to the advantage of the pathogen. Despite the crucial role of globular domains as mediators of protein-protein interactions (PPIs), previous structural studies of bacterial effectors are primarily focused on individual domains, rather than domain-mediated PPIs, which limits their ability to uncover systems-level molecular recognition principles governing host-bacteria interactions. Here, we took an interaction-centric approach and systematically examined the potential of structural components within bacterial proteins to engage in or target eukaryote-specific domain-domain interactions (DDIs). Our results indicate that: 1) effectors are about six times as likely as non-effectors to contain host-like domains that mediate DDIs exclusively in eukaryotes; 2) the average domain in effectors is about seven times as likely as that in non-effectors to co-occur with DDI partners in eukaryotes rather than in bacteria; and 3) effectors are about nine times as likely as non-effectors to contain bacteria-exclusive domains that target host domains mediating DDIs exclusively in eukaryotes. Moreover, in the absence of host-like domains or among pathogen proteins without domain assignment, effectors harbor a higher variety and density of short linear motifs targeting host domains that mediate DDIs exclusively in eukaryotes. Our study lends novel quantitative insight into the structural basis of effector-induced perturbation of host-endogenous PPIs and may aid in the design of selective inhibitors of host-pathogen interactions.

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