MASP3

Background

The complement lectin pathway is activated by binding of recognition proteins, such as mannose-binding lectin (MBL) or ficolins, to an array of carbohydrates on the pathogen surface. Mannose-associated serine proteases (MASPs) have been proved to be an integral part of this initial complement activation process. So far, 3 distinct MASPs (MASP-1, MASP-2, and MASP-3) and two non-catalytic derivatives MAp19 (MBL-associated protein of 19 kDa) and MAp44, have been identified.

MASP-3 and MAp44 are encoded by the MASP1 gene by alternative splicing, which is highly similar to MASP-1 in structure. Human MASP-3 is a single-chain polypeptide with 728 amino acid residues. Both MASP-3 and MASP-1 consist of 6 discrete domains, CUB1 (C1r/C1s, urchin-EGF, and bone morphogenetic protein-1) domain, epidermal growth factor (EGF)-like domain, CUB2 domain, two complement control proteins (CCPs), and serine protease domain from N-terminus to C-terminus. MASP-3 only differs from MASP-1 in the preceding 15 amino acids of C-terminal serine protease domain and has identified five N-terminal domains to MASP-1. Like other MASPs, the CUB1 and CUB2 domains can bind to the recognition molecules, the two CCPs involve in substrate recognition, and the serine protease domain is the catalytic domain.

MASP-3 plays a different role to MASP-1 and MASP-2 since it is unable to cleave complement components C2 and C4. Previous studies have demonstrated that MASP-3 cannot be activated and had no catalytic activity, instead, it competed with MASP-1 and MASP-2 to bind to recognition proteins, playing a regulatory role in the complement lectin pathway activation. Laster researched indicated that MASP-3 played important roles in complement pro-factor D maturation, and could activate factor D and factor B in the complement alternative pathway. MASP-1 or MASP-3 deficiency results in the 3MC syndrome, a disorder characterized by unusual facial features and affecting other tissues and organs.

Fig. 1 Modular architecture of the C1r/C1s/MASP protein family and their function in complement pathway initiation.¹

MASP3 Functional Service

Creative Biolabs delivers an extensive array of MASP3-centered products, including anti-MASP3 antibodies, ELISA kits, human complement MASP3 proteins, and MASP3 Protein Lysate. These meticulously designed instruments are pivotal in propelling research efforts focused on formulating therapeutic approaches for a range of diseases.

Fig.2 Surface plasmon resonance analysis of MASP-3 inhibitor and MASP-3 binding interaction.²

Researchers have discovered that MASP-3 acts as a competitive inhibitor of MASP-2 for MBL binding, initially categorizing it as a negative regulator of the complement system. Investigations with knockout mice suggest that MASP-1 and MASP-3 may be crucial for the activation of complement pro-factor D (pro-FD), despite inconsistent results in human subjects lacking MASP-1 and MASP-3. In resting blood, where coagulation and complement activation are inactive, factor D mostly remains in its active form, indicating an unknown pro-FD activator outside of coagulation or complement initiation. Researchers developed a specific MASP-3 inhibitor and found that all MASPs can activate pro-FD in vitro, but only MASP-3 fulfills this role exclusively in resting blood, connecting the lectin and alternative pathways.

Creative Biolabs provides a diverse portfolio of MASP3-related services, including binding evaluations and supplementary functional investigations, meticulously tailored to support our distinguished clients in both clinical and research settings.

References

1. Gaboriaud, Christine, et al. "The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin." PLoS One 8.7 (2013): e67962.
2. Dobó, József, et al. "MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked." Scientific reports 6.1 (2016): 31877. Distributed under Open Access license CC BY 4.0, without modification.