{"doi":"10.1002/mbo3.1252","title":"Binding of the kringle‐2 domain of human plasminogen to streptococcal PAM‐type M‐protein causes dissociation of PAM dimers","abstract":"Abstract The direct binding of human plasminogen (hPg), via its kringle‐2 domain (K2 hPg ), to streptococcal M‐protein (PAM), largely contributes to the pathogenesis of Pattern D Group A Streptococcus pyogenes (GAS). However, the mechanism of complex formation is unknown. In a system consisting of a Class II PAM from Pattern D GAS isolate NS88.2 (PAM NS88.2 ), with one K2 hPg binding a‐repeat in its A‐domain, we employed biophysical techniques to analyze the mechanism of the K2 hPg /PAM NS88.2 interaction. We show that apo‐PAM NS88.2 is a coiled‐coil homodimer (M.Wt. ~80 kDa) at 4°C–25°C, and is monomeric (M.Wt. ~40 kDa) at 37°C, demonstrating a temperature‐dependent dissociation of PAM NS88.2 over a narrow temperature range. PAM NS88.2 displayed a single tight binding site for K2 hPg at 4°C, which progressively increased at 25°C through 37°C. We isolated the K2 hPg /PAM NS88.2 complexes at 4°C, 25°C, and 37°C and found molecular weights of ~50 kDa at each temperature, corresponding to a 1:1 (m:m) K2 hPg /PAM NS88.2 monomer complex. hPg activation experiments by streptokinase demonstrated that the hPg/PAM NS88.2 monomer complexes are fully functional. The data show that PAM dimers dissociate into functional monomers at physiological temperatures or when presented with the active hPg module (K2 hPg ) showing that PAM is a functional monomer at 37°C.","journal":"MicrobiologyOpen","year":2021,"id":207079,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9647,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":425919,"name":"Yetunde A. Ayinuola","orcid":"0000-0001-7803-8058","position":1,"is_corresponding":false},{"id":792159,"name":"Cunjia Qiu","orcid":"0009-0004-9513-8025","position":2,"is_corresponding":false},{"id":305825,"name":"Shaun W. Lee","orcid":"0000-0001-9305-2050","position":3,"is_corresponding":false},{"id":393199,"name":"Victoria A. Ploplis","orcid":"0000-0002-6506-764X","position":4,"is_corresponding":false},{"id":393200,"name":"Francis Castellino","orcid":"0000-0003-0317-9539","position":5,"is_corresponding":false},{"id":444533,"name":"Olawole Ayinuola","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:51:45.688025Z","pmid":"34964287","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}