The interaction between complement fragment C3d and complement receptor 2 (CR2) is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of -1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic "hot-spots". Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic "hot-spots" at the two functional sites of C3d, while the surface of CR2 lacks electrostatic "hot-spots" despite its excessively positive nature. We propose that the electrostatic "hot-spots" of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2), which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3d, after the divergence of jawless fish.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531323 | PMC |
| http://dx.doi.org/10.1371/journal.pcbi.1002840 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ultrasensitive detection of methylene blue by surface-enhanced Raman scattering (SERS) with Ag nanoparticle-decorated magnetic CoNi layered double hydroxides.
Anal Methods
January 2025
Key Laboratory of Oil and Gas Fine Chemicals Ministry of Education, Xinjiang Uyghur Autonomous Region, School of Chemical Engineering and Technology, Xinjiang University, Urumqi 830017, Xinjiang, China.
The unreasonable use of organic dye leads to excessive residues in environmental water, which seriously threatens human health and the natural environment. In this paper, a spherical flower-like magnetic FeO@CoNi layered double hydroxide@silver nanoparticle (FeO@CoNi LDH@Ag NPs) SERS substrate was successfully fabricated electrostatic self-assembly and applied for the sensitive detection of methylene blue (MB) in environmental water. The rapid concentration and separation of the SERS substrate from the water sample could be achieved using an external magnet.
View Article and Find Full Text PDFStructural commonalities determined by physicochemical principles in the complex polymorphism of the amyloid state of proteins.
Biochem J
January 2025
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Biochemistry, University of Florence, 50134 Florence, Italy.
Advances in solid-state nuclear magnetic resonance (ssNMR) spectroscopy and cryogenic electron microscopy (cryoEM) have revealed the polymorphic nature of the amyloid state of proteins. Given the association of amyloid with protein misfolding disorders, it is important to understand the principles underlying this polymorphism. To address this problem, we combined computational tools to predict the specific regions of the sequence forming the β-spine of amyloid fibrils with the availability of 30, 83 and 24 amyloid structures deposited in the Protein Data Bank (PDB) and Amyloid Atlas (AAt) for the amyloid β (Aβ) peptide, α-synuclein (αS), and the 4R isoforms of tau, associated with Alzheimer's disease, Parkinson's disease, and various tauopathies, respectively.
View Article and Find Full Text PDFTris(2,2'-bipyridine)ruthenium(II)-silver nanoparticle electrostatic nanoaggregates (AgNPs@[Ru(bpy)] ENAs) as novel SERS nanotags for rapid, sensitive and selective immunosensing.
Talanta
April 2025
MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China. Electronic address:
Tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy)]), as a versatile molecule, has been widely applied in various fields, such as photocatalysis, electrochemiluminescence and fluorescence probes, solar cell and LED due to its excellent optical and electrical properties, good water solubility, high chemical stability. In this work, we prepared electrostatic nanoaggregates from [Ru(bpy)] and silver nanoparticles (AgNPs@[Ru(bpy)] ENAs) as a new type of SERS nanotags. Each [Ru(bpy)] ion carries two positive charges with strong affinity to negative surfaces, which enables a strong electrostatic interaction between [Ru(bpy)] and negatively charged silver nanoparticles (AgNPs) and fast (within 10 min) formation of AgNPs@[Ru(bpy)] ENAs.
View Article and Find Full Text PDFStrong electrostatic attraction drives milk heteroprotein complex coacervation.
Int J Biol Macromol
January 2025
Division of Computational Chemistry, Lund University, Naturvetarvägen 24, SE-223 62 Lund, Sweden; LINXS - Institute of advanced Neutron and X-ray Science, Lund University, Scheelevägen 19, 223 70 SE-Lund, Sweden. Electronic address:
Coacervates of oppositely charged milk proteins are used in functional food development, mainly to encapsulate bioactives. To uncover the driving forces behind coacervates formation, we study the association of lactoferrin and β-lactoglobulin at amino-acid level detail, using molecular simulations. Our findings show that inter-protein electrostatic interactions dominate and are, surprisingly, equally divided between an isotropic part, due to monopole-monopole attraction of the oppositely charged proteins, and an anisotropic part due to uneven surface charge distributions.
View Article and Find Full Text PDFWith the rapid development of nanoscience and nanotechnology, surface-enhanced Raman spectroscopy (SERS) is widely used for the detection of analyte molecules and biomolecules in liquids. However, due to the plasmonic near-field effect, the key challenge of SERS detection in liquids is to attract target molecules in solutions into the plasmonic "hot spots". In this work, the SERS-active substrates (Ag@AAO) with excellent signal sensitivity and uniformity were successfully prepared by sputtering Ag films on anodized aluminum oxide (AAO) templates.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!