4fxl: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of the D76N Beta-2 Microglobulin mutant== | |||
<StructureSection load='4fxl' size='340' side='right' caption='[[4fxl]], [[Resolution|resolution]] 1.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4fxl]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FXL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FXL FirstGlance]. <br> | |||
==Disease== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">B2M, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4fxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fxl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fxl RCSB], [http://www.ebi.ac.uk/pdbsum/4fxl PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn variant beta(2)-microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type beta(2)-microglobulin, the affected members of this kindred had normal renal function and normal circulating beta(2)-microglobulin values. The Asp76Asn beta(2)-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of beta(2)-microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the beta(2)-microglobulin variant, including its 1.40-A, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding. | |||
Hereditary systemic amyloidosis due to Asp76Asn variant beta2-microglobulin.,Valleix S, Gillmore JD, Bridoux F, Mangione PP, Dogan A, Nedelec B, Boimard M, Touchard G, Goujon JM, Lacombe C, Lozeron P, Adams D, Lacroix C, Maisonobe T, Plante-Bordeneuve V, Vrana JA, Theis JD, Giorgetti S, Porcari R, Ricagno S, Bolognesi M, Stoppini M, Delpech M, Pepys MB, Hawkins PN, Bellotti V N Engl J Med. 2012 Jun 14;366(24):2276-83. PMID:22693999<ref>PMID:22693999</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Beta-2 microglobulin|Beta-2 microglobulin]] | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Bellotti, V | [[Category: Bellotti, V]] | ||
[[Category: Bolognesi, M | [[Category: Bolognesi, M]] | ||
[[Category: Pepys, M B | [[Category: Pepys, M B]] | ||
[[Category: Ricagno, S | [[Category: Ricagno, S]] | ||
[[Category: Stoppini, M | [[Category: Stoppini, M]] | ||
[[Category: Amyloidosis]] | [[Category: Amyloidosis]] | ||
[[Category: Beta-sandwitch]] | [[Category: Beta-sandwitch]] | ||
