Mapping the mutational landscape for streptokinase binding to plasminogen.

Srishti Baid, Matthew L Holding, Taylor Laurin, David Siemieniak, David Ginsburg, Laura M Haynes

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Article in Journal of thrombosis and haemostasis : JTH, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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Update of
Mapping the Mutational Landscape for Streptokinase Binding to Plasminogen.2026

5 · Who and what money

Authors and funding

6 authors.

Srishti BaidLife Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.

Matthew L HoldingLife Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA; Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, USA.

Taylor LaurinLife Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.

David SiemieniakLife Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.

David GinsburgLife Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA; Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: hayneslm@umich.edu.

Laura M HaynesLife Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: hayneslm@umich.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGroup A Streptococcus (GAS) expresses streptokinase (SK), a critical virulence factor that nonenzymatically activates the host's plasminogen (PLG) to an active form (PLG

objectivesGAS SK is highly specific for human PLG, and sequence variation among SKs from different GAS strains has been linked to differences in PLG binding and disease severity. The contributions of individual amino acids to these differences remain poorly understood.

methodsWe used phage display and deep mutational scanning to map how amino acid substitutions in SK from Group C Streptococcus (GCS), which shares high sequence homology with GAS, affect its ability to bind human PLG.

resultsWe demonstrate that SK, expressed as a fusion protein with the p3 coat protein of the M13 filamentous phage, retains its ability to bind human PLG. Deep mutational scanning mapped 71% of all possible single amino acid substitutions within SK, identifying specific regions where substitutions are likely to increase or decrease its affinity for PLG.

conclusionOur findings suggest a complex protein-protein interaction in which long-range protein dynamics influence the conformational activation of PLG to PLG

Indexed as

fibrinolysishost-pathogen interactionsplasminogenStreptococcusstreptokinase

Identifiers

PMID42710811

DOI10.1016/j.jtha.2026.09.003

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.