RGD Reference Report - Crystal structure of the native plasminogen reveals an activation-resistant compact conformation. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Crystal structure of the native plasminogen reveals an activation-resistant compact conformation.

Authors: Xue, Y  Bodin, C  Olsson, K 
Citation: Xue Y, etal., J Thromb Haemost. 2012 Jul;10(7):1385-96. doi: 10.1111/j.1538-7836.2012.04765.x.
RGD ID: 11528578
Pubmed: PMID:22540246   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1538-7836.2012.04765.x   (Journal Full-text)

BACKGROUND: Plasminogen is the zymogen form of plasmin and the precursor of angiostatin. It has been implicated in a variety of disease states, including thrombosis, bleeding and cancers. The native plasminogen, known as Glu-plasminogen, contains seven domains comprising the N-terminal peptide domain (NTP), five kringle domains (K1-K5) and the C-terminal serine protease domain (SP). Previous studies have established that the lysine binding site (LBS) of the conserved kringle domains plays a crucial role in mediating the regulation of plasminogen function. However, details of the related conformational mechanism are unknown. OBJECTIVES: We aim to understand in more detail the conformational mechanism of plasminogen activation involving the kringles. METHODS: We crystallized the native plasminogen under physiologically relevant conditions and determined the structure at 3.5 A resolution. We performed structural analyses and related these to the literature data to gain critical understanding of the plasminogen activation. RESULTS AND CONCLUSIONS: The structure reveals the precise architecture of the quaternary complex. It shows that the Glu-plasminogen renders its compact form as an activation-resistant conformation for the proteolytic activation. The LBSs of all kringles, except K1, are engaged in intra-molecular interactions while only K1-LBS is readily available for ligand binding or receptor anchorage. The structure also provides insights into the interactions between plasminogen and alpha2-antiplasmin, the primary physiological inhibitor of plasmin. Furthermore, the data presented explain why a conformational transition to the open form is necessary for plasminogen activation as well as angiostatin generation, and provide a rationale for the functional hierarchy of the different kringles.


Additional Information