International Journal of Science and Research (IJSR) ISSN (Online): 2319-7064 Index Copernicus Value (2015): 78.96 | Impact Factor (2015): 6.391 Volume 6 Issue 4, April 2017 www.ijsr.net Licensed Under Creative Commons Attribution CC BY Role of Mannose Binding Lectin and their associated Srine Protease in innate immunity Pankaj Kumar Patel 1 , Bavita Kohli 2 , Krishnan Hajela 3 1 School of Life Sciences, Devi Ahilya University Indore, Khandawa Road Indore 452001 India 2 Department of Biotechnology, IPS Academy, AB road, Rau Indore 452001 India 3 School of Life Sciences, Devi Ahilya University Indore, Khandawa Road Indore 452001 India Abstract: Mannose binding Lectin (MBL) is a key pattern recognition receptor molecule, found in invertebrates to higher vertebrates, MBL initiates various immune and immunomodulatory responses on binding with the pathogen associated molecular patterns (PAMPs). MBL recognizes a wide variety of viruses, bacteria, protozoa, fungi and cell debris opsonizing and clearing them either by opsonophagocytosis or activating complement pathway through MASP-1/2 mediated cleavage of complement components C4 and C2, thus generating the C3 convertase C4bC2b. A new insight on the responses, their mechanism and role of MBL associated serine proteases are discussed in the review. Keywords: Mannose binding Lectin, Complement pathway, Pentraxin, Lectin pathway, MASP 1. Introduction The core function of the immune system are recognition and efficient removal of the pathogens with self-tolerance. The recognition of pathogen and self-tolerance are so crucial for the body that it has developed an array of receptors to monitor and control the immune responses. The innate system represents the first line of defence to an intruding pathogen. The response evolved is therefore rapid, and is unable to memorise the same said pathogen should the body be exposed to it in the future, also it evolved in such a way that it eliminates pathogens while limiting autoimmune response and excessive inflammation. The soluble proteins and phagocyte cells are major component of innate immunity and effector mechanisms. One of the groups of proteins involved in innate immune responses is collectins, family of proteins named so because they contain collagen- like domain and calcium-dependent lectin domains. Collectin is a family of conserved C-type lectins, and the major effectors proteins of innate immune responses; since, these can recognize pathogen-associated molecular patterns on foreign organisms through their carbohydrate recognition domain. The trimeric CRDs can recognize carbohydrate or charge patterns on microbes, allergens, and dying cells while the collagen region can interact with receptor molecules present on a variety of immune cells in order to initiate clearance mechanisms. Once bound with the foreign particle it elicitis appropriate responses by activation of multiple processes of innate immunity such as agglutination, complement activation, opsonization, direct microbicidal action, regulation of inflammation, orchestration of adaptive immunity, interaction with allergens and apoptotic clearance. The members of group includes mannan-binding lectin (MBL), lung surfactant protein A (SP-A), lung surfactant protein D (SP-D), conglutinin, collectin of 43 kDa (CL-43) and collection of 46 kDa (CL-4)(1). 2. Mannose Bindings Lectin MBL belongs to c-type receptor family collectins. The MBL molecules built from 32kd polypeptide chains, encompassing four regions; C-terminal carbohydrate recognition domain (CRD), an alpha helical hydrophobic neck, a collagenous region with 19 glycine-X-Y repeats (where X,Y may be any amino acid) and cysteine rich N- terminal region(2,3). The tri-peptide monomer subunits are formed and stabilized by the hydrophobic bonds and inter chain disulphide linkage within the N-terminal cysteine rich region. MBL exist in oligomeric forms ranging from diamer to hexamers to form a tulip-like structure. Inter-subunit disulfide bond in N-terminal linker region have been shown to be responsible for the association of monomer subunits into oligomeric forms (2). MBL binds with mannose moieties by its C-terminal CRD with low affinity, but the multiple binding of CRDs increase the affinity by several order of magnitude (4). The α-helical coiled domain (hub and swivel region) provides flexibility to the orientation of the CRD to recognize terminal hydroxyl group present in certain sugars like D-mannose and L-fucose (5–7) Structural studies have demonstrated that three sugar binding site of one MBL subunit (i.e. the triple helix) are separated in a constant distance (45 in humans), offering a flat platform to recognize multiple sugar simultaneously (4,6). The clustering of triple helix (higher order oligomers) can further provides wider interface, permitting bindings of multiple CRDs to the array of sugar structures on microbial surface. The serum MBL level is determined genetically by three point mutation in exon-1 of human MBL gene located at codon 52, 54 and 57 (referred as B, D and C respectively while the wild type is referred as A) (8). The mutation results in substitution of amino acids in collagen-like domain resulting in decrease of functional serum MBL concentration Paper ID: ART20172170 620