Crystal structure of the mouse innate immunity factor bacterial permeability-increasing family member A1

Bacterial permeability-increasing family member A1 (BPIFA1) is an innate immunity factor and one of the most abundantly secreted proteins in the upper airways. BPIFA1 is multifunctional, with antimicrobial, surfactant and lipopolysaccharide-binding activities, as well as established roles in lung hydration. Here, the 2.5 Å resolution crystal structure of BPIFA1 from Mus musculus (mBPIFA1) is presented and compared with those of human BPIFA1 (hBPIFA1) and structural homologs. Structural distinctions between mBPIFA1 and hBPIFA1 suggest potential differences in biological function, including the regulation of a key pulmonary ion channel.

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The Crystal Structure of Lipopolysaccharide Binding Protein Reveals the Location of a Frequent Mutation that Impairs Innate Immunity

Immunity ◽

10.1016/j.immuni.2013.09.005 ◽

2013 ◽

Vol 39 (4) ◽

pp. 647-660 ◽

Cited By ~ 57

Author(s):

Jana K. Eckert ◽

Young J. Kim ◽

Jung I. Kim ◽

Kathleen Gürtler ◽

Djin-Ye Oh ◽

...

Keyword(s):

Crystal Structure ◽

Innate Immunity ◽

Binding Protein ◽

Frequent Mutation ◽

Lipopolysaccharide Binding Protein ◽

Lipopolysaccharide Binding

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Mucosal innate immunity of the upper airways in children with recurrent bacterial ENT infections

10.26226/morressier.5afd6e2dd64f25002cfc365e ◽

2018 ◽

Author(s):

Olha Shvaratska

Keyword(s):

Innate Immunity ◽

Upper Airways

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Faculty Opinions recommendation of Crystal structure of the galectin-9 N-terminal carbohydrate recognition domain from Mus musculus reveals the basic mechanism of carbohydrate recognition.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1046241.496173 ◽

2006 ◽

Author(s):

Richard L Stevens

Keyword(s):

Crystal Structure ◽

Mus Musculus ◽

Basic Mechanism ◽

Carbohydrate Recognition Domain ◽

Carbohydrate Recognition

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Humoral factors of innate immunity in the saliva of patients with infectious inflammatory respiratory diseases

OTORHINOLARYNGOLOGY 2-3(2) 2019 - OTORHINOLARYNGOLOGY ◽

10.37219/2528-8253-2018-2-13 ◽

2018 ◽

pp. 13-17

Author(s):

Oleg Melnikov ◽

Diana Zabolotnaya ◽

Alexander Bredun ◽

Bogdan Bil ◽

Oksana Rylska ◽

...

Keyword(s):

Innate Immunity ◽

Chronic Rhinosinusitis ◽

Inflammatory Diseases ◽

Activity Level ◽

Chronic Tonsillitis ◽

Control Group ◽

Quantitative Composition ◽

Upper Airways ◽

Humoral Factors ◽

Immune Modulators

Introduction: In recently ears factors of innate immunity both cellular and humoral have been paid considerable attention as they are a protective barrier of a fast response and that is why they are largely concentrated at the intersection of the digestive tract and airways. The data concerning the activity level of factors of innate immunity in the upper airways affected by nonspecific inflammatory processes is insufficient and sparse and therefore the purpose of this research was to study the content of humoral factors of innate immunity in the oropharyngeal secretion (ORS) of patients with chronic infectious inflammatory diseases of the upper airways in remission. Materials and Methods: There was an examination of 16 patients with chronic rhinosinusitis (CRS) of bacterial genesis (15-40 years old), 12 patients with rhinopharyngitis of post-viral genesis (8-16 years old), 12 people with scleroma from 30 tо 52 years of age (atrophic form), 10 patients with chronic tonsillitis in remission (from 10 to 33 years of age) and 11 patients of a control group (practically healthy donors from 12 tо 40 years of age). The content of MIP-1b, defensin-1β, lactoferrin, lysozyme, α-interferon was studied in the nonstimulated OPS. Statistics were carried out using Mann-Whitney U-test. Results: The greatest number of deviations in the decrease in the content of the examined nonspecific protective factors was found in cases of scleroma, chronic tonsillitis and chronic rhinosinusitis (p<0,05). The lack of protective humoral factors of innate immunity can be evidence of local immunodeficiency even in remission, which is a pathophysiological component of the maintenance of chronic inflammation. Conclusion: The decrease int he quantitative composition of factors of innate immunity in the oropharyngeal secretion of patients with chronic infectious inflammatory diseases of the airways is an objective ground not only for a replacement therapy, but also for the use of immune response modifiers from photo-immune modulators to “genuine immune modulators” controlling the state of the factors of both innate immunity and immunoglobulins, primarily of secretory type, the level and functionality of various groups of immunocompetent and accessory cells.

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Structural basis for ligand and innate immunity factor uptake by the trypanosome haptoglobin-haemoglobin receptor

eLife ◽

10.7554/elife.05553 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 22

Author(s):

Harriet Lane-Serff ◽

Paula MacGregor ◽

Edward D Lowe ◽

Mark Carrington ◽

Matthew K Higgins

Keyword(s):

Innate Immunity ◽

Trypanosoma Brucei ◽

Molecular Basis ◽

Structural Basis ◽

Β Subunit ◽

Trypanosome Infection ◽

Lateral Mobility ◽

African Trypanosomes ◽

Distal Half ◽

Immunity Factor

The haptoglobin-haemoglobin receptor (HpHbR) of African trypanosomes allows acquisition of haem and provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. In this study, we report the structure of Trypanosoma brucei HpHbR in complex with human haptoglobin-haemoglobin (HpHb), revealing an elongated ligand-binding site that extends along its membrane distal half. This contacts haptoglobin and the β-subunit of haemoglobin, showing how the receptor selectively binds HpHb over individual components. Lateral mobility of the glycosylphosphatidylinositol-anchored HpHbR, and a ∼50o kink in the receptor, allows two receptors to simultaneously bind one HpHb dimer. Indeed, trypanosomes take up dimeric HpHb at significantly lower concentrations than monomeric HpHb, due to increased ligand avidity that comes from bivalent binding. The structure therefore reveals the molecular basis for ligand and innate immunity factor uptake by trypanosomes and identifies adaptations that allow efficient ligand uptake in the context of the complex trypanosome cell surface.

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Mechanism of ligand binding – PDZ domain taken as example

Bio-Algorithms and Med-Systems ◽

10.1515/bams-2017-0022 ◽

2017 ◽

Vol 13 (4) ◽

Author(s):

Dawid Dułak ◽

Mateusz Banach ◽

Zdzisław Wiśniowski ◽

Leszek Konieczny ◽

Irena Roterman

Keyword(s):

Crystal Structure ◽

Ligand Binding ◽

Ion Channel ◽

Pdz Domain ◽

Traditional Model ◽

Beta Sheet ◽

Hydrophobic Core ◽

Beta Strand ◽

Model Based ◽

Specific Ligand

AbstractThe mechanism of specific ligand binding by proteins is discussed using the PDZ domain complexing the pentapeptide. This process is critical for clustering the membrane ion channel. The traditional model based on the Beta-sheet extension by complexed pentapeptide is interpreted as a hydrophobic core extension supported by additional Beta-strand generated by complexed pentapeptide. The explanation is based on the fuzzy oil drop model applied to the crystal structure of PDZ-pentapeptide.

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