Crystal Structure of a Polymeric Immunoglobulin Binding Fragment of the Human Polymeric Immunoglobulin Receptor

Hamburger, Agnes E.; West, Anthony P.; Björkman, Pamela J.

doi:10.1016/j.str.2004.09.006

Cited by 97 publications

(98 citation statements)

References 72 publications

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“…A similar topology was determined in the modeling of domains 2 and 3 (D2 and D3) of mouse SC (16). These were confirmed by the crystal structure of D1 of human SC, which revealed a V-type fold (17). So far, the three-dimensional domain arrangement of full-length SC has not been considered, even though this is essential to appreciate molecular mechanisms that are involved in mucosal immunity.…”

mentioning

confidence: 79%

“…Molecular modeling and crystal structures of SC domains from rabbit, mouse, and human have already contributed insight into the topology of SC and pIgA complexes (14,15,17). However, the analyses of only protein fragments, the use of strictly predictive computer-based modeling, and the absence of information on carbohydrate residues all represent limitations when compared with the determination of the three-dimensional structure of fulllength SC.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the cleavage in the D1-D3 sample, the similarity of these three lengths is explained by postulating that SC is folded back upon itself. If the end-toend length of the SC domains is taken to be 3.7 nm from the D1 crystal structure (17), SC, D1-D3, and D4 -D5 are predicted to be 18.5, 11.1, and 7.4 nm long if they are fully extended but with no linkers. The disparity between the observed SC length of 10.6 -11.9 nm and the 18.5 nm prediction shows that SC must be folded back.…”

Section: Characterization Of Sc and Itsmentioning

confidence: 99%

“…1. The homology modeling of D2-D5 employed MODELLER v7 (24) and was based on a topological sequence alignment with the D1 crystal structure identified using BLASTP (PDB code 1xed) (17). The models were structurally validated using PROCHECK.…”

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confidence: 99%

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Solution Structure of Human Secretory Component and Implications for Biological Function

Bonner

Perrier

Corthésy

et al. 2007

Journal of Biological Chemistry

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Secretory component (SC) in association with polymeric IgA (pIgA) forms secretory IgA, the major antibody active at mucosal surfaces. SC also exists in the free form, with innate-like neutralizing properties against pathogens. Free SC consists of five glycosylated variable (V)-type Ig domains (D1-D5), whose structure was determined by x-ray and neutron scattering, ultracentrifugation, and modeling. With a radius of gyration of 3.53-3.63 nm, a length of 12.5 nm, and a sedimentation coefficient of 4.0 S, SC possesses an unexpected compact structure. Constrained scattering modeling based on up to 13,000 trial models shows that SC adopts a J-shaped structure in which D4 and D5 are folded back against D2 and D3. The seven glycosylation sites are located on one side of SC, leaving known IgAbinding motifs free to interact with pIgA. This work represents the first analysis of the three-dimensional structure of fulllength free SC and paves the way to a better understanding of the association between SC and its potential ligands, i.e. pIgA and pathogenic-associated motifs.The mucosal epithelia lining the gastrointestinal, respiratory, and urogenital tracts represent the largest surface (400 m 2 for the human body) in contact with the external environment (1). Consequently, they are permanently exposed to foreign antigens and must therefore be efficiently protected to prevent possible damage by pathogenic agents (2). In response to this threat, a major immune defense system is mediated by secretory immunoglobulin A (SIgA) 5 within the lumen (3), where SIgA exerts its function of antigen neutralization. IgA is produced locally as polymeric IgA (pIgA), which consists of two or four IgA molecules linked covalently by a J chain (4). Subsequent transport of pIgA (and to a lesser extent pentameric IgM) across the epithelium is ensured by the polymeric Ig receptor (pIgR), which is expressed on the basolateral surface of epithelial cells. Following cleavage at luminal surfaces, SIgA is released as a complex of pIgA and the cleaved extracellular portion of the pIgR which is termed secretory component (SC). Because secretory IgM can be present in external secretions with an accessory role as a neutralizing antibody, this suggests that SC has a generic antibody-binding ability, being able to bind to both pIgA and pentameric IgM (5). This selectivity may be required to allow only larger, polymerized antibodies protected by heavily glycosylated SCs to enter the harsh environment of external secretions.SC consists of five immunoglobulin-like domains (D1-D5) and up to seven glycan chains. SC bound to pIgA protects the antibody against proteolytic digestion (6) and governs anchoring of SIgA at mucosal surfaces (7). Free SC is also found in secretions and is now recognized as an active antibacterial participant to protect mucosal surfaces against Helicobacter pylori (8), enteropathogenic Escherichia coli and Clostridium difficile toxin A (9), and Streptococcus pneumoniae choline binding protein A (10, 11). Recombinant human SC produced fro...

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mentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Characterization Of Sc and Itsmentioning

confidence: 99%

mentioning

confidence: 99%

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Solution Structure of Human Secretory Component and Implications for Biological Function

Bonner

Perrier

Corthésy

et al. 2007

Journal of Biological Chemistry

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“…Notably, a large number of the Ig domains identified using types I and II domain query sequences appear to possess distinct second disulfide bonds at the corresponding C-C′ beta strand region (Cantoni et al 2003;Hamburger et al 2004) as well as Ig V-set signature residues and lengths. In addition, the amino acid motif KYWC, which is found at the conserved IgSF tryptophan residue in the type I and most of the type II domains of skate MDIRs, is also found in the IgSF domain of the Fcα/µ receptor (Shibuya et al 2000) and in various domains of mammalian pIgRs and CMRF-35/MAIR/CLM (Fig.…”

Section: Mdirs Are a Large And Diverse Set Of Igsf Molecules That Likmentioning

confidence: 99%

Ancient divergence of a complex family of immune-type receptor genes

et al. 2006

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Multigene families of activating/inhibitory receptors belonging to the immunoglobulin superfamily (IgSF) regulate immunological and other cell-cell interactions. A new family of such genes, termed modular domain immune-type receptors (MDIRs), has been identified in the clearnose skate (Raja eglanteria), a phylogenetically ancient vertebrate. At least five different major forms of predicted MDIR proteins are comprised of four different subfamilies of IgSF ectodomains of the intermediate (I)-or C2-set. The predicted number of individual IgSF ectodomains in MDIRs varies from one to six. MDIR1 contains a positively charged transmembrane residue and MDIR2 and MDIR3 each possesses at least one immunoreceptor tyrosine-based inhibitory motif in their cytoplasmic regions. MDIR4 and MDIR5 lack characteristic activating/inhibitory signalling motifs. MDIRs are encoded in a particularly large and complex multigene family. MDIR domains exhibit distant sequence similarity to mammalian CMRF-35-like molecules, polymeric immunoglobulin receptors, triggering receptors expressed on myeloid cells (TREMs), TREM-like transcripts, NKp44 and FcR homologs, as well as to sequences identified in several different vertebrate genomes. Phylogenetic analyses suggest that MDIRs are representative members of an extended family of IgSF genes that diverged before or very early in evolution of the vertebrates and subsequently came to occupy multiple, fully independent distributions in the present day.

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Survey of the year 2004 commercial optical biosensor literature

Rich

Myszka

2005

J of Molecular Recognition

114

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The year 2004 represents a milestone for the biosensor research community: in this year, over 1000 articles were published describing experiments performed using commercially available systems. The 1038 papers we found represent a $ 10% increase over the past year and demonstrate that the implementation of biosensors continues to expand at a healthy pace. We evaluated the data presented in each paper and compiled a 'top 10' list. These 10 articles, which we recommend every biosensor user reads, describe wellperformed kinetic, equilibrium and qualitative/screening studies, provide comparisons between binding parameters obtained from different biosensor users, as well as from biosensor-and solution-based interaction analyses, and summarize the cutting-edge applications of the technology. We also re-iterate some of the experimental pitfalls that lead to sub-optimal data and over-interpreted results. We are hopeful that the biosensor community, by applying the hints we outline, will obtain data on a par with that presented in the 10 spotlighted articles. This will ensure that the scientific community at large can be confident in the data we report from optical biosensors.

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Crystal Structure of a Polymeric Immunoglobulin Binding Fragment of the Human Polymeric Immunoglobulin Receptor

Cited by 97 publications

References 72 publications

Solution Structure of Human Secretory Component and Implications for Biological Function

Solution Structure of Human Secretory Component and Implications for Biological Function

Ancient divergence of a complex family of immune-type receptor genes

Survey of the year 2004 commercial optical biosensor literature

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