PDBsum entry 3cm9

Immune system

PDB id: 3cm9

Contents

Protein chains

462 a.a.* *

106 a.a.* *

214 a.a.* *

585 a.a.* *

* Residue conservation analysis

* C-alpha coords only

PDB id:

3cm9

Name:

Immune system

Title:

Solution structure of human siga2

Structure:

Immunoglobulin heavy chain. Chain: a, b, c, d. Secretory component. Chain: j. Fragment: ig-like v-type domain 4. Immunoglobulin light chain. Chain: l, m, n, o. Secretory component. Chain: s

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: purified from human colostrum. Other_details: purified from human colostrum

Ensemble:

10 models

Authors:

A.Bonner,A.Almogren,P.B.Furtado,M.A.Kerr,S.J.Perkins

Key ref:

A.Bonner et al. (2009). The nonplanar secretory IgA2 and near planar secretory IgA1 solution structures rationalize their different mucosal immune responses. J Biol Chem, 284, 5077-5087. PubMed id: 19109255 DOI: 10.1074/jbc.M807529200

Date:

21-Mar-08 Release date: 30-Dec-08

Protein chains

No UniProt id for this chain

Struc: 462 a.a.

Protein chain

P01833  (PIGR_HUMAN) -  Polymeric immunoglobulin receptor from Homo sapiens

Seq: 764 a.a.

Struc: 106 a.a.*

Protein chains

No UniProt id for this chain

Struc: 214 a.a.

Protein chain

P01833  (PIGR_HUMAN) -  Polymeric immunoglobulin receptor from Homo sapiens

Seq: 764 a.a.

Struc: 585 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains J, S: E.C.?

DOI no: 10.1074/jbc.M807529200

J Biol Chem 284:5077-5087 (2009)

PubMed id: 19109255

The nonplanar secretory IgA2 and near planar secretory IgA1 solution structures rationalize their different mucosal immune responses.

A.Bonner, A.Almogren, P.B.Furtado, M.A.Kerr, S.J.Perkins.

ABSTRACT

Secretory IgA (SIgA) is the most prevalent human antibody and is central to mucosal immunity. It exists as two subclasses, SIgA1 and SIgA2, where SIgA2 has a shorter hinge joining the Fab and Fc regions. Both forms of SIgA are predominantly dimeric and contain an additional protein called the secretory component (SC) that is attached during the secretory process and is believed to protect SIgA in harsh mucosal conditions. Here we locate the five SC domains relative to dimeric IgA2 within SIgA2 using constrained scattering modeling. The x-ray and sedimentation parameters showed that SIgA2 has an extended solution structure. The constrained modeling of SIgA2 was initiated using two IgA2 monomers that were positioned according to our best fit solution structure for dimeric IgA1. SC was best located along the convex edge of the Fc-Fc region. The best fit models showed that SIgA2 is significantly nonplanar in its structure, in distinction to our previous near planar SIgA1 structure. Both the shorter IgA2 hinges and the presence of SC appear to displace the four Fab regions out of the Fc plane in SIgA2. This may explain the noncovalent binding of SC in some SIgA2 molecules. This nonplanar structure is predicted to result in specific immune properties for SIgA2 and SIgA1. It may explain differences observed between the SIgA1 and SIgA2 subclasses in terms of their interactions with antigens, susceptibility to proteases, effects on receptors, and distribution in different tissues. The different structures account for the prevalence of both forms in mucosal secretions.

Selected figure(s)

Figure 1.
Domain structure of SIgA2. SIgA2 is shown as two IgA2m(1) monomers, a J chain, and a secretory component (domains D1–D5). Each IgA2 heavy chain contains the V[H], C[H]1, C[H]2, and C[H]3 domains. Each light chain contains the V[L] and C[L] domains. The complementarity-determining regions (CDR), the 13-residue hinge and the 18-residue C-terminal tailpiece are highlighted. The IgA2m(2) allotype does not have a Cys^214–Cys^214 disulfide bridge. The possible interheavy chain disulfide bridges at Cys^241, Cys^242, Cys^299, and Cys^301 are denoted by an extended X. Cys^471 in one tailpiece of each Fc region is disulfide-bridged with either Cys^15 or Cys^68 in the J chain, which is located on the convex edge of the Fc-Fc region. A Cys^311–Cys^502 bridge between the C[H]2 and D5 domains is shown. N-Linked oligosaccharide sites are denoted by filled symbols (•).

Figure 7.
Survey of best fit models for SIgA2 from Cycle 2. Comparison of the x-ray R factors with the R[G] and R[XS] values for 3000 models based on the randomization of the Fab regions. The dashed lines indicate the experimental x-ray R[G], R[XS-1], and R[XS-2]values.

The above figures are reprinted from an Open Access publication published by the ASBMB: J Biol Chem (2009, 284, 5077-5087) copyright 2009.

Figures were selected by an automated process.