8wys

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Local map of human CD5L bound to IgM-Fc/J

Structural highlights

8wys is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.41Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IL2_HUMAN Note=A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17.IGHM_HUMAN Autosomal agammaglobulinemia. The disease is caused by mutations affecting the gene represented in this entry.^[1]

Function

IL2_HUMAN Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells.IGHM_HUMAN IgM antibodies play an important role in primary defense mechanisms. They have been shown to be involved in early recognition of external invaders like bacteria and viruses, cellular waste and modified self, as well as in recognition and elimination of precancerous and cancerous lesions. The membrane-bound form is found in the majority of normal B-cells alongside with IgD. Membrane-bound IgM induces the phosphorylation of CD79A and CD79B by the Src family of protein tyrosine kinases. It may cause death of cells by apoptosis. It is also found in soluble form, which represents about 30% of the total serum immunoglobulins where it is found almost exclusively as a homopentamer. After the antigen binds to the B-cell receptor, the secreted form is secreted in large amounts.^[2]

Publication Abstract from PubMed

CD5 antigen-like (CD5L), also known as Spalpha or AIM (Apoptosis inhibitor of macrophage), emerges as an integral component of serum immunoglobulin M (IgM). However, the molecular mechanism underlying the interaction between IgM and CD5L has remained elusive. In this study, we present a cryo-electron microscopy structure of the human IgM pentamer core in complex with CD5L. Our findings reveal that CD5L binds to the joining chain (J chain) in a Ca(2+)-dependent manner and further links to IgM via a disulfide bond. We further corroborate recently published data that CD5L reduces IgM binding to the mucosal transport receptor pIgR, but does not impact the binding of the IgM-specific receptor FcmuR. Additionally, CD5L does not interfere with IgM-mediated complement activation. These results offer a more comprehensive understanding of IgM and shed light on the function of the J chain in the immune system.

CD5L associates with IgM via the J chain.,Wang Y, Su C, Ji C, Xiao J Nat Commun. 2024 Sep 27;15(1):8397. doi: 10.1038/s41467-024-52175-y. PMID:39333069^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trubel H, Pachman LM, Kitchingman GR, Campana D, Rohrer J, Conley ME. Mutations in the mu heavy-chain gene in patients with agammaglobulinemia. N Engl J Med. 1996 Nov 14;335(20):1486-93. PMID:8890099 doi:http://dx.doi.org/10.1056/NEJM199611143352003
↑ Tisch R, Roifman CM, Hozumi N. Functional differences between immunoglobulins M and D expressed on the surface of an immature B-cell line. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6914-8. PMID:3137579
↑ Wang Y, Su C, Ji C, Xiao J. CD5L associates with IgM via the J chain. Nat Commun. 2024 Sep 27;15(1):8397. PMID:39333069 doi:10.1038/s41467-024-52175-y