scholarly journals Structural analysis of protein–protein interactions in type I polyketide synthases

2012 ◽  
Vol 48 (2) ◽  
pp. 98-122 ◽  
Author(s):  
Wei Xu ◽  
Kangjian Qiao ◽  
Yi Tang
Keyword(s):  
Structural Analysis ◽  
Protein Interactions ◽  
Polyketide Synthases ◽  
Type I ◽  
Protein Protein Interactions

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

2019 ◽  
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 ◽  
Polyketide Synthases ◽  
Combinatorial Biosynthesis ◽  
Prediction Algorithm ◽  
Type I ◽  
Protein Protein Interactions ◽  
Assembly Lines

AbstractPolyketide synthases are multimodular enzymes that generate diverse molecules of great pharmaceutical importance, including a range of clinically used antimicrobials and antitumor agents. Many polyketides are synthesized by type I polyketide synthases (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. 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. Here, we introduce PKSpop, which uses a coevolution-based protein-protein interaction prediction algorithm to infer protein order in PKS assembly lines. Our method accurately predicts protein orders (80% 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 protein-protein interactions than coevolution between ketosynthase and acyl carrier protein domains.

scholarly journals TRIM22. A Multitasking Antiviral Factor

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1864
Author(s):  
Isabel Pagani ◽  
Guido Poli ◽  
Elisa Vicenzi
Keyword(s):  
Protein Interactions ◽  
Influenza A ◽  
Direct Interaction ◽  
Type I Interferons ◽  
Viral Gene ◽  
Target Cells ◽  
Type I ◽  
Protein Protein Interactions ◽  
Viral Genomes ◽  
Dna And Rna

Viral invasion of target cells triggers an immediate intracellular host defense system aimed at preventing further propagation of the virus. Viral genomes or early products of viral replication are sensed by a number of pattern recognition receptors, leading to the synthesis and production of type I interferons (IFNs) that, in turn, activate a cascade of IFN-stimulated genes (ISGs) with antiviral functions. Among these, several members of the tripartite motif (TRIM) family are antiviral executors. This article will focus, in particular, on TRIM22 as an example of a multitarget antiviral member of the TRIM family. The antiviral activities of TRIM22 against different DNA and RNA viruses, particularly human immunodeficiency virus type 1 (HIV-1) and influenza A virus (IAV), will be discussed. TRIM22 restriction of virus replication can involve either direct interaction of TRIM22 E3 ubiquitin ligase activity with viral proteins, or indirect protein–protein interactions resulting in control of viral gene transcription, but also epigenetic effects exerted at the chromatin level.

An activity-based probe reveals dynamic protein–protein interactions mediating IGF-1R transactivation by the GABAB receptor

2012 ◽  
Vol 443 (3) ◽  
pp. 627-634 ◽  
Author(s):  
Xin Lin ◽  
Xin Li ◽  
Ming Jiang ◽  
Linhai Chen ◽  
Chanjuan Xu ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Complex ◽  
Tyrosine Kinases ◽  
Chemical Biology ◽  
Molecular Mechanisms ◽  
Gabab Receptor ◽  
Type I ◽  
Protein Protein Interactions ◽  
Downstream Effectors ◽  
Factor Type

Many GPCRs (G-protein-coupled receptors) can activate RTKs (receptor tyrosine kinases) in the absence of RTK ligands, a phenomenon called transactivation. However, the underlying molecular mechanisms remain undefined. In the present study we investigate the molecular basis of GABAB (γ-aminobutyric acid B) receptor-mediated transactivation of IGF-1R (insulin-like growth factor type I receptor) in primary neurons. We take a chemical biology approach by developing an activity-based probe targeting the GABAB receptor. This probe enables us first to lock the GABAB receptor in an inactive state and then activate it with a positive allosteric modulator, thereby permitting monitoring of the dynamic of the protein complex associated with IGF-1R transactivation. We find that activation of the GABAB receptor induces a dynamic assembly and disassembly of a protein complex, including both receptors and their downstream effectors. FAK (focal adhesion kinase), a non-RTK, plays a key role in co-ordinating this dynamic process. Importantly, this dynamic of the GABAB receptor-associated complex is critical for transactivation and transactivation-dependent neuronal survival. The present study has identified an important mechanism underlying GPCR transactivation of RTKs, which was enabled by a new chemical biology tool generally applicable for dissecting GPCR signalling.

scholarly journals Dynamic rewiring of the human interactome by interferon signalling

2019 ◽  
Author(s):  
Craig H. Kerr ◽  
Michael A. Skinnider ◽  
Angel M. Madero ◽  
Daniel D.T. Andrews ◽  
R. Greg Stacey ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Interaction Network ◽  
Cell Types ◽  
Antiviral Response ◽  
Type I ◽  
Protein Protein Interactions ◽  
Human Interactome ◽  
Viral Pathogens ◽  
Protein Protein Interaction ◽  
Dependent Protein

ABSTRACTBackgroundThe type I interferon (IFN) response is an ancient pathway that protects cells against viral pathogens by inducing the transcription of hundreds of IFN-stimulated genes (ISGs). Transcriptomic and biochemical approaches have established comprehensive catalogues of ISGs across species and cell types, but their antiviral mechanisms remain incompletely characterized. Here, we apply a combination of quantitative proteomic approaches to delineate the effects of IFN signalling on the human proteome, culminating in the use of protein correlation profiling to map IFN-induced rearrangements in the human protein-protein interaction network.ResultsWe identified >27,000 protein interactions in IFN-stimulated and unstimulated cells, many of which involve proteins associated with human disease and are observed exclusively within the IFN-stimulated network. Differential network analysis reveals interaction rewiring across a surprisingly broad spectrum of cellular pathways in the antiviral response. We identify IFN-dependent protein-protein interactions mediating novel regulatory mechanisms at the transcriptional and translational levels, with one such interaction modulating the transcriptional activity of STAT1. Moreover, we reveal IFN-dependent changes in ribosomal composition that act to buffer ISG protein synthesis.ConclusionsOur map of the IFN interactome provides a global view of the complex cellular networks activated during the antiviral response, placing ISGs in a functional context, and serves as a framework to understand how these networks are dysregulated in autoimmune or inflammatory disease.

scholarly journals Structure of the Q237W mutant of HhaI DNA methyltransferase: an insight into protein-protein interactions

2004 ◽  
Vol 385 (5) ◽  
pp. 373-379 ◽  
Author(s):  
A. Dong ◽  
L. Zhou ◽  
X. Zhang ◽  
S. Stickel ◽  
R.J. Roberts ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Active Sites ◽  
Dna Methyltransferase ◽  
Monoclinic Space Group ◽  
Type I ◽  
Protein Protein Interactions ◽  
Mutant Proteins ◽  
Dimer Interface ◽  
Space Groups ◽  
Carboxy Terminal

Abstract We have determined the structure of a mutant (Q237W) of HhaI DNA methyltransferase, complexed with the methyl-donor product AdoHcy. The Q237W mutant proteins were crystallized in the monoclinic space group C2 with two molecules in the crystallographic asymmetric unit. Protein-protein interface calculations in the crystal lattices suggest that the dimer interface has the specific characteristics for homodimer protein-protein interactions, while the two active sites are spatially independent on the outer surface of the dimer. The solution behavior suggests the formation of HhaI dimers as well. The same HhaI dimer interface is also observed in the previously characterized binary (M.HhaIAdoMet) and ternary (M.HhaIDNAAdoHcy) complex structures, crystallized in different space groups. The dimer is characterized either by a noncrystallographic two-fold symmetry or a crystallographic symmetry. The dimer interface involves three segments: the aminoterminal residues 28, the carboxyterminal residues 313327, and the linker (amino acids 179184) between the two functional domains the catalytic methylation domain and the DNA target recognition domain. Both the amino- and carboxy-terminal segments are part of the methylation domain. We also examined proteinprotein interactions of other structurally characterized DNA MTases, which are often found as a 2-fold related dimer with the largest dimer interface area for the group-β MTases. A possible evolutionary link between the Type I and Type II restriction-modification systems is discussed.

scholarly journals Engineering strategies for rational polyketide synthase design

2018 ◽  
Vol 35 (10) ◽  
pp. 1070-1081 ◽  
Author(s):  
Maja Klaus ◽  
Martin Grininger
Keyword(s):  
Protein Interactions ◽  
Assembly Line ◽  
Polyketide Synthase ◽  
Polyketide Synthases ◽  
Protein Protein Interactions ◽  
Important Protein ◽  
Line P

In this review, we highlight strategies in engineering polyketide synthases (PKSs). We focus on important protein–protein interactions that constitute an intact PKS assembly line.

scholarly journals Protein–protein interactions in “cis-AT” polyketide synthases

2018 ◽  
Vol 35 (10) ◽  
pp. 1082-1096 ◽  
Author(s):  
Greg J. Dodge ◽  
Finn P. Maloney ◽  
Janet L. Smith
Keyword(s):  
Protein Interactions ◽  
Active Site ◽  
Catalytic Domain ◽  
Polyketide Synthases ◽  
Protein Protein Interactions ◽  
P Protein ◽  
In Cis

Protein–protein interactions of cis-AT polyketide synthases are dominated by the travels of the ACP domain to the active site entrance of each catalytic domain.

A structural network associated with the kallikrein-kinin and renin-angiotensin systems

2010 ◽  
Vol 391 (4) ◽  
Author(s):  
Veronika Stoka ◽  
Vito Turk
Keyword(s):  
Protein Interactions ◽  
Three Dimensional ◽  
Type I ◽  
Protein Protein Interactions ◽  
Renin Angiotensin ◽  
Protein Protein Interaction ◽  
Protein Interfaces ◽  
Structural Network ◽  
Domain Interactions ◽  
Fibronectin Type

Abstract The kallikrein-kinin and renin-angiotensin (KKS-RAS) systems represent two highly regulated proteolytic systems that are involved in several physiological and pathological processes. Although their protein-protein interactions can be studied using experimental approaches, it is difficult to differentiate between direct physical interactions and functional associations, which do not involve direct atomic contacts between macromolecules. This information can be obtained from an atomic-resolution characterization of the protein interfaces. As a result of this, various three-dimensional-based protein-protein interaction databases have become available. To gain insight into the multilayered interaction of the KKS-RAS systems, we present a protein network that is built up on three-dimensional domain-domain interactions. The essential domains that link these systems are as follows: Cystatin, Peptidase_C1, Thyroglobulin_1, Insulin, CIMR (Cation-independent mannose-6-phosphate receptor repeat), fn2 (Fibronectin type II domain), fn1 (Fibronectin type I domain), EGF, Trypsin, and Serpin. We found that the CIMR domain is located at the core of the network, thus connecting both systems. From the latter, all domain interactors up to level 4 were retrieved, thus displaying a more comprehensive representation of the KKS-RAS structural network.

scholarly journals A split protease-E. coli ClpXP system quantifies protein–protein interactions in Escherichia coli cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shengchen Wang ◽  
Faying Zhang ◽  
Meng Mei ◽  
Ting Wang ◽  
Yueli Yun ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
High Efficiency ◽  
Cellular Protein ◽  
Type I ◽  
Protein Protein Interactions ◽  
E Coli ◽  
Protein Protein Interaction ◽  
Quantitative Fluorescence ◽  
Temperature Adaptability

AbstractCharacterizing protein–protein interactions (PPIs) is an effective method to help explore protein function. Here, through integrating a newly identified split human Rhinovirus 3 C (HRV 3 C) protease, super-folder GFP (sfGFP), and ClpXP-SsrA protein degradation machinery, we developed a fluorescence-assisted single-cell methodology (split protease-E. coli ClpXP (SPEC)) to explore protein–protein interactions for both eukaryotic and prokaryotic species in E. coli cells. We firstly identified a highly efficient split HRV 3 C protease with high re-assembly ability and then incorporated it into the SPEC method. The SPEC method could convert the cellular protein-protein interaction to quantitative fluorescence signals through a split HRV 3 C protease-mediated proteolytic reaction with high efficiency and broad temperature adaptability. Using SPEC method, we explored the interactions among effectors of representative type I-E and I-F CRISPR/Cas complexes, which combining with subsequent studies of Cas3 mutations conferred further understanding of the functions and structures of CRISPR/Cas complexes.

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