3wjj

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'''Unreleased structure'''
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{{STRUCTURE_3wjj| PDB=3wjj | SCENE= }}
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===Crystal structure of IIb selective Fc variant, Fc(P238D), in complex with FcgRIIb===
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{{ABSTRACT_PUBMED_23744091}}
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The entry 3wjj is ON HOLD
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==Disease==
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[[http://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[http://omim.org/entry/254500 254500]]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4. [[http://www.uniprot.org/uniprot/FCG2B_HUMAN FCG2B_HUMAN]] Note=A chromosomal aberration involving FCGR2B is found in a follicular lymphoma. Translocation t(1;22)(q22;q11). The translocation leads to the hyperexpression of the receptor. This may play a role in the tumor progression. Defects in FCGR2B are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:[http://omim.org/entry/152700 152700]]. A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.<ref>PMID:12115230</ref> <ref>PMID:20385827</ref>
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Authors: Kadono, S., Mimoto, F., Katada, H., Igawa, T., Kuramochi, T., Muraoka, M., Wada, Y., Haraya, K., Miyazaki, T., Hattori, K.
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==Function==
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[[http://www.uniprot.org/uniprot/FCG2B_HUMAN FCG2B_HUMAN]] Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis.
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Description: Crystal structure of IIb selective Fc variant, Fc(P238D), in complex with FcgRIIb
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==About this Structure==
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[[3wjj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WJJ OCA].
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==Reference==
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<ref group="xtra">PMID:023744091</ref><references group="xtra"/><references/>
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[[Category: Haraya, K.]]
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[[Category: Hattori, K.]]
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[[Category: Igawa, T.]]
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[[Category: Kadono, S.]]
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[[Category: Katada, H.]]
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[[Category: Kuramochi, T.]]
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[[Category: Mimoto, F.]]
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[[Category: Miyazaki, T.]]
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[[Category: Muraoka, M.]]
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[[Category: Wada, Y.]]
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[[Category: Antibody]]
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[[Category: Fc receptor]]
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[[Category: Immune system]]
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[[Category: Receptor complex]]

Revision as of 08:19, 13 November 2013

Template:STRUCTURE 3wjj

Contents

Crystal structure of IIb selective Fc variant, Fc(P238D), in complex with FcgRIIb

Template:ABSTRACT PUBMED 23744091

Disease

[IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:254500]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4. [FCG2B_HUMAN] Note=A chromosomal aberration involving FCGR2B is found in a follicular lymphoma. Translocation t(1;22)(q22;q11). The translocation leads to the hyperexpression of the receptor. This may play a role in the tumor progression. Defects in FCGR2B are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.[1] [2]

Function

[FCG2B_HUMAN] Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis.

About this Structure

3wjj is a 3 chain structure. Full crystallographic information is available from OCA.

Reference

  • Mimoto F, Katada H, Kadono S, Igawa T, Kuramochi T, Muraoka M, Wada Y, Haraya K, Miyazaki T, Hattori K. Engineered antibody Fc variant with selectively enhanced FcgammaRIIb binding over both FcgammaRIIa(R131) and FcgammaRIIa(H131). Protein Eng Des Sel. 2013 Oct;26(10):589-98. doi: 10.1093/protein/gzt022. Epub, 2013 Jun 5. PMID:23744091 doi:http://dx.doi.org/10.1093/protein/gzt022
  1. ↑ Kyogoku C, Dijstelbloem HM, Tsuchiya N, Hatta Y, Kato H, Yamaguchi A, Fukazawa T, Jansen MD, Hashimoto H, van de Winkel JG, Kallenberg CG, Tokunaga K. Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility. Arthritis Rheum. 2002 May;46(5):1242-54. PMID:12115230 doi:10.1002/art.10257
  2. ↑ Willcocks LC, Carr EJ, Niederer HA, Rayner TF, Williams TN, Yang W, Scott JA, Urban BC, Peshu N, Vyse TJ, Lau YL, Lyons PA, Smith KG. A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7881-5. doi:, 10.1073/pnas.0915133107. Epub 2010 Apr 12. PMID:20385827 doi:10.1073/pnas.0915133107

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