9i5n: Difference between revisions

Latest revision as of 07:34, 25 February 2026

Single particle cryo electron microscopy of a Fab fragment bound to recombinant human CD40 ligand

Structural highlights

9i5n is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.4Å
Ligands:	MG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CD40L_HUMAN Defects in CD40LG are the cause of X-linked immunodeficiency with hyper-IgM type 1 (HIGM1) [MIM:308230; also known as X-linked hyper IgM syndrome (XHIM). HIGM1 is an immunoglobulin isotype switch defect characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including Pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Function

CD40L_HUMAN Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL-4. Involved in immunoglobulin class switching.^[11] Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and an matrix metalloproteinases (MMP) inhibitor-sensitive pathway.^[12]

References

↑ Aruffo A, Farrington M, Hollenbaugh D, Li X, Milatovich A, Nonoyama S, Bajorath J, Grosmaire LS, Stenkamp R, Neubauer M, et al.. The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Cell. 1993 Jan 29;72(2):291-300. PMID:7678782
↑ Korthauer U, Graf D, Mages HW, Briere F, Padayachee M, Malcolm S, Ugazio AG, Notarangelo LD, Levinsky RJ, Kroczek RA. Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature. 1993 Feb 11;361(6412):539-41. PMID:7679206 doi:https://dx.doi.org/10.1038/361539a0
↑ DiSanto JP, Bonnefoy JY, Gauchat JF, Fischer A, de Saint Basile G. CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM. Nature. 1993 Feb 11;361(6412):541-3. PMID:8094231 doi:https://dx.doi.org/10.1038/361541a0
↑ Allen RC, Armitage RJ, Conley ME, Rosenblatt H, Jenkins NA, Copeland NG, Bedell MA, Edelhoff S, Disteche CM, Simoneaux DK, et al.. CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome. Science. 1993 Feb 12;259(5097):990-3. PMID:7679801
↑ Macchi P, Villa A, Strina D, Sacco MG, Morali F, Brugnoni D, Giliani S, Mantuano E, Fasth A, Andersson B, et al.. Characterization of nine novel mutations in the CD40 ligand gene in patients with X-linked hyper IgM syndrome of various ancestry. Am J Hum Genet. 1995 Apr;56(4):898-906. PMID:7717401
↑ Saiki O, Tanaka T, Wada Y, Uda H, Inoue A, Katada Y, Izeki M, Iwata M, Nunoi H, Matsuda I, et al.. Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM. J Clin Invest. 1995 Feb;95(2):510-4. PMID:7532185 doi:https://dx.doi.org/10.1172/JCI117692
↑ Katz F, Hinshelwood S, Rutland P, Jones A, Kinnon C, Morgan G. Mutation analysis in CD40 ligand deficiency leading to X-linked hypogammaglobulinemia with hyper IgM syndrome. Hum Mutat. 1996;8(3):223-8. PMID:8889581 doi:<223::AID-HUMU5>3.0.CO;2-A 10.1002/(SICI)1098-1004(1996)8:3<223::AID-HUMU5>3.0.CO;2-A
↑ Lin Q, Rohrer J, Allen RC, Larche M, Greene JM, Shigeoka AO, Gatti RA, Derauf DC, Belmont JW, Conley ME. A single strand conformation polymorphism study of CD40 ligand. Efficient mutation analysis and carrier detection for X-linked hyper IgM syndrome. J Clin Invest. 1996 Jan 1;97(1):196-201. PMID:8550833 doi:https://dx.doi.org/10.1172/JCI118389
↑ Nonoyama S, Shimadzu M, Toru H, Seyama K, Nunoi H, Neubauer M, Yata J, Och HD. Mutations of the CD40 ligand gene in 13 Japanese patients with X-linked hyper-IgM syndrome. Hum Genet. 1997 May;99(5):624-7. PMID:9150729
↑ Seyama K, Nonoyama S, Gangsaas I, Hollenbaugh D, Pabst HF, Aruffo A, Ochs HD. Mutations of the CD40 ligand gene and its effect on CD40 ligand expression in patients with X-linked hyper IgM syndrome. Blood. 1998 Oct 1;92(7):2421-34. PMID:9746782
↑ Furman MI, Krueger LA, Linden MD, Barnard MR, Frelinger AL 3rd, Michelson AD. Release of soluble CD40L from platelets is regulated by glycoprotein IIb/IIIa and actin polymerization. J Am Coll Cardiol. 2004 Jun 16;43(12):2319-25. PMID:15193700 doi:10.1016/j.jacc.2003.12.055
↑ Furman MI, Krueger LA, Linden MD, Barnard MR, Frelinger AL 3rd, Michelson AD. Release of soluble CD40L from platelets is regulated by glycoprotein IIb/IIIa and actin polymerization. J Am Coll Cardiol. 2004 Jun 16;43(12):2319-25. PMID:15193700 doi:10.1016/j.jacc.2003.12.055

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Aruffo A, Farrington M, Hollenbaugh D, Li X, Milatovich A, Nonoyama S, Bajorath J, Grosmaire LS, Stenkamp R, Neubauer M, et al.. The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Cell. 1993 Jan 29;72(2):291-300. PMID:7678782

[2] Korthauer U, Graf D, Mages HW, Briere F, Padayachee M, Malcolm S, Ugazio AG, Notarangelo LD, Levinsky RJ, Kroczek RA. Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature. 1993 Feb 11;361(6412):539-41. PMID:7679206 doi:https://dx.doi.org/10.1038/361539a0

[3] DiSanto JP, Bonnefoy JY, Gauchat JF, Fischer A, de Saint Basile G. CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM. Nature. 1993 Feb 11;361(6412):541-3. PMID:8094231 doi:https://dx.doi.org/10.1038/361541a0

[4] Allen RC, Armitage RJ, Conley ME, Rosenblatt H, Jenkins NA, Copeland NG, Bedell MA, Edelhoff S, Disteche CM, Simoneaux DK, et al.. CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome. Science. 1993 Feb 12;259(5097):990-3. PMID:7679801

[5] Macchi P, Villa A, Strina D, Sacco MG, Morali F, Brugnoni D, Giliani S, Mantuano E, Fasth A, Andersson B, et al.. Characterization of nine novel mutations in the CD40 ligand gene in patients with X-linked hyper IgM syndrome of various ancestry. Am J Hum Genet. 1995 Apr;56(4):898-906. PMID:7717401

[6] Saiki O, Tanaka T, Wada Y, Uda H, Inoue A, Katada Y, Izeki M, Iwata M, Nunoi H, Matsuda I, et al.. Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM. J Clin Invest. 1995 Feb;95(2):510-4. PMID:7532185 doi:https://dx.doi.org/10.1172/JCI117692

[7] Katz F, Hinshelwood S, Rutland P, Jones A, Kinnon C, Morgan G. Mutation analysis in CD40 ligand deficiency leading to X-linked hypogammaglobulinemia with hyper IgM syndrome. Hum Mutat. 1996;8(3):223-8. PMID:8889581 doi:<223::AID-HUMU5>3.0.CO;2-A 10.1002/(SICI)1098-1004(1996)8:3<223::AID-HUMU5>3.0.CO;2-A

[8] Lin Q, Rohrer J, Allen RC, Larche M, Greene JM, Shigeoka AO, Gatti RA, Derauf DC, Belmont JW, Conley ME. A single strand conformation polymorphism study of CD40 ligand. Efficient mutation analysis and carrier detection for X-linked hyper IgM syndrome. J Clin Invest. 1996 Jan 1;97(1):196-201. PMID:8550833 doi:https://dx.doi.org/10.1172/JCI118389

[9] Nonoyama S, Shimadzu M, Toru H, Seyama K, Nunoi H, Neubauer M, Yata J, Och HD. Mutations of the CD40 ligand gene in 13 Japanese patients with X-linked hyper-IgM syndrome. Hum Genet. 1997 May;99(5):624-7. PMID:9150729

[10] Seyama K, Nonoyama S, Gangsaas I, Hollenbaugh D, Pabst HF, Aruffo A, Ochs HD. Mutations of the CD40 ligand gene and its effect on CD40 ligand expression in patients with X-linked hyper IgM syndrome. Blood. 1998 Oct 1;92(7):2421-34. PMID:9746782

[11] Furman MI, Krueger LA, Linden MD, Barnard MR, Frelinger AL 3rd, Michelson AD. Release of soluble CD40L from platelets is regulated by glycoprotein IIb/IIIa and actin polymerization. J Am Coll Cardiol. 2004 Jun 16;43(12):2319-25. PMID:15193700 doi:10.1016/j.jacc.2003.12.055

[12] Furman MI, Krueger LA, Linden MD, Barnard MR, Frelinger AL 3rd, Michelson AD. Release of soluble CD40L from platelets is regulated by glycoprotein IIb/IIIa and actin polymerization. J Am Coll Cardiol. 2004 Jun 16;43(12):2319-25. PMID:15193700 doi:10.1016/j.jacc.2003.12.055

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9i5n is ON HOLD  until Paper Publication
+==Single particle cryo electron microscopy of a Fab fragment bound to recombinant human CD40 ligand==
+<StructureSection load='9i5n' size='340' side='right'caption='[[9i5n]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
-Authors: Kristoffersen, E.L., Schinkel, T., Andersen, E.S.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9i5n]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9I5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9I5N FirstGlance]. <br>
-Description: Single particle cryo electron microscopy of a Fab fragment bound to recombinant human CD40 ligand
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-[[Category: Schinkel, T]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9i5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9i5n OCA], [https://pdbe.org/9i5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9i5n RCSB], [https://www.ebi.ac.uk/pdbsum/9i5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9i5n ProSAT]</span></td></tr>
-[[Category: Kristoffersen, E.L]]
+</table>
-[[Category: Andersen, E.S]]
+== Disease ==
+[https://www.uniprot.org/uniprot/CD40L_HUMAN CD40L_HUMAN] Defects in CD40LG are the cause of X-linked immunodeficiency with hyper-IgM type 1 (HIGM1) [MIM:[https://omim.org/entry/308230 308230]; also known as X-linked hyper IgM syndrome (XHIM). HIGM1 is an immunoglobulin isotype switch defect characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including Pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence.<ref>PMID:7678782</ref> <ref>PMID:7679206</ref> <ref>PMID:8094231</ref> <ref>PMID:7679801</ref> <ref>PMID:7717401</ref> <ref>PMID:7532185</ref> <ref>PMID:8889581</ref> <ref>PMID:8550833</ref> <ref>PMID:9150729</ref> <ref>PMID:9746782</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/CD40L_HUMAN CD40L_HUMAN] Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL-4. Involved in immunoglobulin class switching.<ref>PMID:15193700</ref>   Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and an matrix metalloproteinases (MMP) inhibitor-sensitive pathway.<ref>PMID:15193700</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Andersen ES]]
+[[Category: Kristoffersen EL]]
+[[Category: Schinkel T]]

9i5n: Difference between revisions

Latest revision as of 07:34, 25 February 2026

Single particle cryo electron microscopy of a Fab fragment bound to recombinant human CD40 ligand

Structural highlights

Disease

Function

References

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