Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Putting the structure into complement.

ABSTRACT: In a field where structure has finally begun to have a real impact, a series of new structures over the last two years have further extended our understanding of some of the critical regulatory events of the complement system. Notably, information has begun to flow from larger assemblies of components which allow insight into the often transient assemblies critical to complement regulation at the cell surface. This review will summarise the key structures determined since the last International Complement Workshop and the insights these have given us, before highlighting some questions that still require molecular frameworks to drive understanding.

SUBMITTER: Lea SM

PROVIDER: S-EPMC3664973 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Putting the structure into complement.

Lea Susan M SM Johnson Steven S

Immunobiology 20121101 11

In a field where structure has finally begun to have a real impact, a series of new structures over the last two years have further extended our understanding of some of the critical regulatory events of the complement system. Notably, information has begun to flow from larger assemblies of components which allow insight into the often transient assemblies critical to complement regulation at the cell surface. This review will summarise the key structures determined since the last International ...[more]

PMID: 22964238

Similar Datasets

Putting on molecular weight: Enabling cryo-EM structure determination of sub-100-kDa proteins.

Project description:Significant advances in the past decade have enabled high-resolution structure determination of a vast variety of proteins by cryogenic electron microscopy single particle analysis. Despite improved sample preparation, next-generation imaging hardware, and advanced single particle analysis algorithms, small proteins remain elusive for reconstruction due to low signal-to-noise and lack of distinctive structural features. Multiple efforts have therefore been directed at the development of size-increase techniques for small proteins. Here we review the latest methods for increasing effective molecular weight of proteins <100 kDa through target protein binding or target protein fusion - specifically by using nanobody-based assemblies, fusion tags, and symmetric scaffolds. Finally, we summarize these state-of-the-art techniques into a decision-tree to facilitate the design of tailored future approaches, and thus for further exploration of ever-smaller proteins that make up the largest part of the human genome.

| S-EPMC9562432 | biostudies-literature

Putting structure into context: fitting of atomic models into electron microscopic and electron tomographic reconstructions.

Project description:A complete understanding of complex dynamic cellular processes such as cell migration or cell adhesion requires the integration of atomic level structural information into the larger cellular context. While direct atomic-level information at the cellular level remains inaccessible, electron microscopy, electron tomography and their associated computational image processing approaches have now matured to a point where sub-cellular structures can be imaged in three dimensions at the nanometer scale. Atomic-resolution information obtained by other means can be combined with this data to obtain three-dimensional models of large macromolecular assemblies in their cellular context. This article summarizes some recent advances in this field.

| S-EPMC3294126 | biostudies-literature

Putting data integration into practice: using biomedical terminologies to add structure to existing data sources.

Project description:A major purpose of biomedical terminologies is to provide uniform concept representation, allowing for improved methods of analysis of biomedical information. While this goal is being realized in bioinformatics, with the emergence of the Gene Ontology as a standard, there is still no real standard for the representation of clinical concepts. As discoveries in biology and clinical medicine move from parallel to intersecting paths, standardized representation will become more important. A large portion of significant data, however, is mainly represented as free text, upon which conducting computer-based inferencing is nearly impossible. In order to test our hypothesis that existing biomedical terminologies, specifically the UMLS Metathesaurus and SNOMED CT, could be used as templates to implement semantic and logical relationships over free text data that is important both clinically and biologically, we chose to analyze OMIM (Online Mendelian Inheritance in Man). After finding OMIM entries' conceptual equivalents in each respective terminology, we extracted the semantic relationships that were present and evaluated a subset of them for semantic, logical, and biological legitimacy. Our study reveals the possibility of putting the knowledge present in biomedical terminologies to its intended use, with potentially clinically significant consequences.

| S-EPMC1480054 | biostudies-literature

Putting p53 in Context.

Project description:TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?

| S-EPMC5743327 | biostudies-literature

Crystal structure of zebrafish complement 1qA globular domain.

Project description:C1q contains three globular domains (C1qgD) that are the key functional component of the classical complement system. C1qgD can interact with important immune molecules, including IgG and C-reactive protein (CRP) to form defense systems to protect animals. Here, the first non-mammalian structure, zebrafish C1qA globular domain (Dare-C1qAgD) was solved. Although the overall architecture of Dare-C1qAgD is similar to human C1qA, residues involved in C1qBgD, C1qCgD, and CRP binding are somewhat different while residues involved in IgG binding are not present in zebrafish. The structure gives insight into how human and fish C1qA evolved from an ancestral protein.

| S-EPMC5029524 | biostudies-literature

Structure of complement fragment C3b-factor H and implications for host protection by complement regulators.

Project description:Factor H (FH) is an abundant regulator of complement activation and protects host cells from self-attack by complement. Here we provide insight into the regulatory activity of FH by solving the crystal structure of the first four domains of FH in complex with its target, complement fragment C3b. FH interacted with multiple domains of C3b, covering a large, extended surface area. The structure indicated that FH destabilizes the C3 convertase by competition and electrostatic repulsion and that FH enables proteolytic degradation of C3b by providing a binding platform for protease factor I while stabilizing the overall domain arrangement of C3b. Our results offer general models for complement regulation and provide structural explanations for disease-related mutations in the genes encoding both FH and C3b.

| S-EPMC2713992 | biostudies-literature

Structure of vaccinia complement protein in complex with heparin and potential implications for complement regulation.

Project description:Vaccinia virus complement control protein (VCP), a homolog of the regulators of the complement activation family of proteins, inhibits complement activation through mechanisms similar to human fluid-phase complement regulators factor H and C4b-binding protein. VCP has a heparin-binding activity that assists vaccinia in host interactions. Interaction with cell-surface polyanions like heparin is centrally important in the functioning of fluid-phase complement regulators and is the basis of host-target discrimination by the alternative pathway. We report the structure of VCP in complex with a heparin decasaccharide, which reveals changes in VCP that might be pertinent to complement regulation. Properties that VCP shares with fluid-phase complement regulators suggest that such conformational changes may be of relevance in the functioning of other complement regulators. Additionally, comparison of VCP-heparin interactions with potentially similar interactions in factor H might enable understanding of the structural basis of familial hemolytic uremic syndrome, attributed to mutational disruption of heparin and C3b binding by factor H.

| S-EPMC428448 | biostudies-literature

Putting social marketing into practice.

Project description: Not available

| S-EPMC1463949 | biostudies-literature

Putting (One's) Heart into Music.

Project description: Not available

| S-EPMC8374961 | biostudies-literature

Putting Mucins on the Map.

Project description: Not available

| S-EPMC6423107 | biostudies-literature