# Leptospira glyceraldehyde-3-phosphate dehydrogenase (LiGAPDH): a cell-surface plasminogen binding protein

## TL;DR

This study shows that a protein from Leptospira can bind to a human blood protein, which may help the bacteria invade and spread in the body.

## Contribution

The paper reports a novel function of Leptospira GAPDH in binding human plasminogen.

## Key findings

- LiGAPDH is surface-exposed and interacts with plasminogen.
- The LiGAPDH-plasmin complex degrades fibrinogen and vitronectin.
- Plasmin bound to LiGAPDH degrades the C5 α-chain but not C3b.

## Abstract

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is classically recognized as a glycolytic enzyme that catalyzes the conversion of glyceraldehyde 3-phosphate into D-glyceryl 1,3-bisphosphate. However, it also exhibits “moonlighting” functions, serving roles unrelated to metabolism. Notably, this multifunctional protein, which lacks a conventional membrane anchor, is present on the surface of many prokaryotic and eukaryotic cells. In this study, we demonstrate that Leptospira interrogans GAPDH (LiGAPDH) is surface-exposed and interacts with plasminogen. In the presence of the exogenous activator uPA, plasminogen is converted into its active form, plasmin. The LiGAPDH-plasmin complex can degrade fibrinogen (α and β chains) and the 75-kDa form of vitronectin over time. Interestingly, plasmin, when bound to LiGAPDH, completely degrades the C5 α-chain but does not affect C3b. The functional characterization of moonlighting proteins and the identification of host molecules they interact with may offer insights for understanding the mechanisms of invasion, dissemination, and immune evasion employed by pathogenic leptospires.

In this study, we report a novel function of GAPDH from Leptospira: its ability to bind human plasminogen, a key component of the host coagulation system.