Identification of a novel plasmin(ogen)‐binding motif in surface displayed α‐enolase of Streptococcus pneumoniae

Abstract

SummaryThe interaction of Streptococcus pneumoniae with human plasmin(ogen) represents a mechanism to enhance bacterial virulence by capturing surfaceassociated proteolytic activity in the infected host. Plasminogen binds to surface displayed pneumococcal a a a a -enolase (Eno) and is subsequently activated to the serine protease plasmin by host-derived tissue plasminogen activator (tPA) or urokinase (uPA).

Characterization of pyruvate dehydrogenase subunit B and enolase as plasminogen-binding proteins in Mycoplasma pneumoniae

“…In most cases, enolases interact with plasminogen but binding to fibronectin and laminin has also been reported (Carneiro et al, 2004;Castaldo et al, 2009;Donofrio et al, 2009). The M. pneumoniae enolase shows typical putative plasminogen-binding sites, such as lysine in the C terminus, 448 FKNIK 452 , and a lysine-rich internal motif, 268 KRYVFKKGIKAKILDEK 284 (Bergmann et al, 2003;Derbise et al, 2004;Yavlovich et al, 2007). A surprising fact was the absence of this enzyme on the surface of mycoplasma cells.…”

“…The dual role of glycolytic enzymes was first described in streptococci (Pancholi & Fischetti, 1992). Meanwhile, these interactions have been reported for phylogenetically different micro-organisms, including fungi, parasites, and Gram-positive and Gramnegative bacteria (Barbosa et al, 2006;Bergmann et al, 2003;Egea et al, 2007;Gozalbo et al 1998;Lama et al, 2009). Furthermore, an increasing number of microbial glycolytic enzymes have been characterized as involved in the interaction with human ECM, such as glyceraldehyde-3-phosphate dehydrogenases (Pancholi & Fischetti, 1992) and enolases (Pancholi & Fischetti, 1998).…”

Plasminogen Substrate Recognition by the Streptokinase-Plasminogen Catalytic Complex Is Facilitated by Arg253, Lys256, and Lys257 in the Streptokinase β-Domain and Kringle 5 of the Substrate

“…In the binding of a 30-residue peptide from plasminogen binding Group A streptococcal M-like protein (PAM), VEK-30, to K2 of Pg, Castellino and co-workers (41,42) showed by crystallography and mutagenesis that residues with cationic (Arg and His) and anionic side chains (Glu) arranged spatially on a helix constituted a pseudolysine structure similar to 6-AHA that binds specifically to the LBS of K2. Additional evidence for pseudolysine structures in Pg binding comes from studies of ␣-enolase from Streptococcus pneumoniae, which has a 9-residue internal binding site for Pg containing essential basic (two Lys residues) and acidic (Asp and Glu residues) located on a surface loop (43,44).…”

Repeating Structures of the Major Staphylococcal Autolysin Are Essential for the Interaction with Human Thrombospondin 1 and Vitronectin

“…Spectroscopy-To analyze direct protein-protein interactions, human TSP-1 was immobilized on a CM5 biosensor (Biacore, GE Healthcare) using amine coupling as described earlier (57). Briefly, the dextran surface was activated with 1-ethyl-3-(3-dimethylpropyl)-carbodiimide (0.2 M) and N-hydroxysuccinimide (0.05 M).…”