Preferential Acquisition and Activation of Plasminogen Glycoform II by PAM Positive Group A Streptococcal Isolates

• DOI: 10.1021/acs.biochem.5b00130
• Publication Date: 2015-06-01T12:51:25Z
• Authors: David M. P. De Ol...; Ruby H. P. Law; Diane Ly; Simon M. Cook; Adam J. Quek; Jason D. McArthur; James C. Whisstock; Martina L. Sander...
• Keywords: Glycosylation; 572; Protein Conformation; Streptococcus pyogenes; Pyogenes; Site; Social and Behavioral Sciences; 03 medical and health sciences; Bacterial Proteins; Kringles; Streptococcal Infections; Medicine and Health Sciences; Humans; Kringle 2; Domain; Surface Protein Pam; Aminocaproates; 0303 health sciences; Binding Sites; Virulence; 500; Plasminogen; Enzyme Activation; High-Affinity Binding; Alpha-Enolase; Human Glu-Plasminogen; Streptokinase Variants; Protein Binding

Plasminogen (Plg) circulates in the host as two predominant glycoforms. Glycoform I Plg (GI-Plg) contains glycosylation sites at Asn289 and Thr346, whereas glycoform II (GII-Plg) is exclusively glycosylated Thr346. Surface plasmon resonance experiments demonstrated that binding group A streptococcal M protein (PAM) exhibits comparative equal affinity for GI- GII-Plg "closed" conformation (for GII-Plg, KD = 27.4 nM; GI-Plg, 37.0 nM). When was "open" conformation, PAM exhibited an 11-fold increase (KD 2.8 nM) compared with GI-Plg 33.2 The interaction of believed to be mediated by lysine within kringle (KR) 2 Plg. PAM-GI-Plg interactions were fully inhibited 100 mM analogue ε-aminocaproic acid (εACA), PAM-GII-Plg shown weakened but not presence 400 εACA. In contrast, KR1-3 domains (angiostatin) completely 5 Along PAM, emm pattern D GAS isolates express a phenotypically distinct SK variant (type 2b SK) requires ligands such activate Type able generate active site rate significantly higher than when bound PAM. Taken together, these data suggest selectively recruits activates GII-Plg. Furthermore, we propose between may partially secondary outside KR2, affected Asn289.