title: Molecular interaction between natural IgG and ficolin--mechanistic insights on adaptive-innate immune crosstalk.
abstract: Recently, we found that natural IgG (nIgG; a non-specific immunoglobulin of adaptive immunity) is not quiescent, but plays a crucial role in immediate immune defense by collaborating with ficolin (an innate immune protein). However, how the nIgG and ficolin interplay and what factors control the complex formation during infection is unknown. Here, we found that mild acidosis and hypocalcaemia induced by infection- inflammation condition increased the nIgG:ficolin complex formation. Hydrogen-deuterium exchange mass spectrometry delineated the binding interfaces to the CH2-CH3 region of nIgG Fc and P-subdomain of ficolin FBG domain. Infection condition exposes novel binding sites. Site-directed mutagenesis and surface plasmon resonance analyses of peptides, derived from nIgG and ficolin, defined the interacting residues between the proteins. These results provide mechanistic insights on the interaction between two molecules representing the adaptive and innate immune pathways, prompting potential development of immunomodulatory/prophylactic peptides tunable to prevailing infection conditions.
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543.
authors.forename: Saswati
authors.initials: S
authors.lastname: Panda
authors.affiliation: 1] NUS graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, 117543 [2].
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 1] Computational and Systems Biology, Singapore-MIT Alliance, 4 Engineering Drive 3, Singapore, 117576 [2].
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543.
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Anand
authors.affiliation: 1] Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543 [2] Computational and Systems Biology, Singapore-MIT Alliance, 4 Engineering Drive 3, Singapore, 117576.
authors.forename: Jeak L
authors.initials: JL
authors.lastname: Ding
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000915:Antibody Affinity; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism; D005260:Female; D006639:Histidine / Q000737:chemistry; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D037102:Lectins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008958:Models, Molecular; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D000097604:Ficolins
chemical_list: D000936:Antigen-Antibody Complex; D015922:Complement C1q; D006639:Histidine; D007074:Immunoglobulin G; D037102:Lectins; D010446:Peptide Fragments; D000097604:Ficolins