Lipoprotein(a) Binds to Recombinant Nontypeable Haemophilus influenzae Aspartase

The respiratory pathogen nontypeable Haemophilus influenza (NTHi) can recruit plasminogen (Plg) on the cell surface by its Plg receptor aspartase (ASP) and utilize host Plg and fibrinolytic system to achieve its adherence and immune invasion. Lipoprotein(a) [Lp(a)] consists of one molecule low-density lipoprotein (LDL) and one molecule apolipoprotein(a) [Apo(a)]. Apo(a) shares a high degree of homology with the human Plg, and both of them contain lysine-binding sites (LBS), which enables them to interact with various cell-surface receptors or fibrin(ogen). However, the definite physiological function of Lp(a) remains vague. Here, we present evidence that Lp(a) via its Apo(a) may bind to thePlg receptor ASP. Recombinant aspartase (rASP) and C-terminal lysine-deleted variant of ASP (rASPΔK) were used in the current study. The rASP specifically bound to Lp(a), but rASPΔK did not, indicating that C-terminal lysine residue of rASP was responsible for the interaction. In addition, rASP interacted with Lp(a), but not with LDL, revealing that LBS of Apo(a) was involved in the binding. Our results also showed that Lp(a) could inhibit the binding of Plg to rASP. Plasma Lp(a) might play a role in anti-NTHi infection by binding to its Plg receptor ASP.