Interaction between matrix metalloproteinase-9 (MMP-9) and neutrophil gelatinase-associated lipocalin (NGAL): A recent evolutionary event in primates

Matrix metallopmteases are known to represent an early step in the evolution of the immune system. Similarly, neutmphil gelatinase-associated lipocalin is known to be a key effector in immune response. MMP-9 interacts with NGAL, but their interaction mechanisms remain unclear. Functional interaction between proteins is ensured by coevolution. Protein coevolution was inferred by calculating the linear correlation coefficients between interprotein distance matrices using MirrorTree. Among examined mammal species, we found a robust signal of MMP-9/NGAL coevolution exclusively within Primates (R = 0.96, p < 1e-06). Owing to the high conservation of these proteins among Mammals, we chose to utilize a recent version of Blocks in Sequences (BIS2) algorithm implemented in BIS2Analyzer webserver. Coevolution clusters between the two proteins were identified in MMP-9 fibronectin and hemopexin domains. Our results suggest that MMP-9/NGAL interaction is a recent evolutionary acquisition in Primates. Furthermore, MMP-9 hemopexin domain would represent a promising target for drug design against these molecules.

Automated summary

The study reveals a strong signal of coevolution between MMP-9 and NGAL exclusively within Primates, shedding light on the functional interaction between proteins in immune evolution. Using linear correlation coefficients to calculate interprotein distance matrices, the study uncovers the coevolution relationship between these proteins.