This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4b3f

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 14:54, 4 August 2016

crystal structure of Ighmbp2 helicase

Structural highlights

4b3f is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1msz, 4b3g
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SMBP2_HUMAN] Defects in IGHMBP2 are the cause of distal hereditary motor neuronopathy type 6 (HMN6) [MIM:604320]; also known as spinal muscular atrophy distal autosomal recessive 1 (DSMA1) or spinal muscular atrophy with respiratory distress 1 (SMARD1). Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. The most prominent symptoms of HMN6 are severe respiratory distress resulting from diaphragmatic paralysis with eventration shown on chest x-ray and predominant involvement of the upper limbs and distal muscles.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Function

[SMBP2_HUMAN] 5' to 3' helicase that unwinds RNA and DNA duplices in an ATP-dependent reaction. Acts as a transcription regulator. Required for the transcriptional activation of the flounder liver-type antifreeze protein gene. Exhibits strong binding specificity to the enhancer element B of the flounder antifreeze protein gene intron. Binds to the insulin II gene RIPE3B enhancer region. May be involved in translation (By similarity). DNA-binding protein specific to 5'-phosphorylated single-stranded guanine-rich sequence related to the immunoglobulin mu chain switch region. Preferentially binds to the 5'-GGGCT-3' motif. Interacts with tRNA-Tyr. Stimulates the transcription of the human neurotropic virus JCV.^[8] ^[9]

Publication Abstract from PubMed

Mutations in immunoglobulin micro-binding protein 2 (Ighmbp2) cause distal spinal muscular atrophy type 1 (DSMA1), an autosomal recessive disease that is clinically characterized by distal limb weakness and respiratory distress. However, despite extensive studies, the mechanism of disease-causing mutations remains elusive. Here we report the crystal structures of the Ighmbp2 helicase core with and without bound RNA. The structures show that the overall fold of Ighmbp2 is very similar to that of Upf1, a key helicase involved in nonsense-mediated mRNA decay. Similar to Upf1, domains 1B and 1C of Ighmbp2 undergo large conformational changes in response to RNA binding, rotating 30 degrees and 10 degrees , respectively. The RNA binding and ATPase activities of Ighmbp2 are further enhanced by the R3H domain, located just downstream of the helicase core. Mapping of the pathogenic mutations of DSMA1 onto the helicase core structure provides a molecular basis for understanding the disease-causing consequences of Ighmbp2 mutations.

The Ighmbp2 helicase structure reveals the molecular basis for disease-causing mutations in DMSA1.,Lim SC, Bowler MW, Lai TF, Song H Nucleic Acids Res. 2012 Sep 10. PMID:22965130^[10]

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

References

↑ Guenther UP, Handoko L, Laggerbauer B, Jablonka S, Chari A, Alzheimer M, Ohmer J, Plottner O, Gehring N, Sickmann A, von Au K, Schuelke M, Fischer U. IGHMBP2 is a ribosome-associated helicase inactive in the neuromuscular disorder distal SMA type 1 (DSMA1). Hum Mol Genet. 2009 Apr 1;18(7):1288-300. doi: 10.1093/hmg/ddp028. Epub 2009 Jan , 20. PMID:19158098 doi:10.1093/hmg/ddp028
↑ Grohmann K, Schuelke M, Diers A, Hoffmann K, Lucke B, Adams C, Bertini E, Leonhardt-Horti H, Muntoni F, Ouvrier R, Pfeufer A, Rossi R, Van Maldergem L, Wilmshurst JM, Wienker TF, Sendtner M, Rudnik-Schoneborn S, Zerres K, Hubner C. Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. Nat Genet. 2001 Sep;29(1):75-7. PMID:11528396 doi:10.1038/ng703
↑ Grohmann K, Varon R, Stolz P, Schuelke M, Janetzki C, Bertini E, Bushby K, Muntoni F, Ouvrier R, Van Maldergem L, Goemans NM, Lochmuller H, Eichholz S, Adams C, Bosch F, Grattan-Smith P, Navarro C, Neitzel H, Polster T, Topaloglu H, Steglich C, Guenther UP, Zerres K, Rudnik-Schoneborn S, Hubner C. Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1). Ann Neurol. 2003 Dec;54(6):719-24. PMID:14681881 doi:10.1002/ana.10755
↑ Maystadt I, Zarhrate M, Landrieu P, Boespflug-Tanguy O, Sukno S, Collignon P, Melki J, Verellen-Dumoulin C, Munnich A, Viollet L. Allelic heterogeneity of SMARD1 at the IGHMBP2 locus. Hum Mutat. 2004 May;23(5):525-6. PMID:15108294 doi:10.1002/humu.9241
↑ Tachi N, Kikuchi S, Kozuka N, Nogami A. A new mutation of IGHMBP2 gene in spinal muscular atrophy with respiratory distress type 1. Pediatr Neurol. 2005 Apr;32(4):288-90. PMID:15797190 doi:10.1016/j.pediatrneurol.2004.11.003
↑ Guenther UP, Varon R, Schlicke M, Dutrannoy V, Volk A, Hubner C, von Au K, Schuelke M. Clinical and mutational profile in spinal muscular atrophy with respiratory distress (SMARD): defining novel phenotypes through hierarchical cluster analysis. Hum Mutat. 2007 Aug;28(8):808-15. PMID:17431882 doi:10.1002/humu.20525
↑ Guenther UP, Handoko L, Varon R, Stephani U, Tsao CY, Mendell JR, Lutzkendorf S, Hubner C, von Au K, Jablonka S, Dittmar G, Heinemann U, Schuetz A, Schuelke M. Clinical variability in distal spinal muscular atrophy type 1 (DSMA1): determination of steady-state IGHMBP2 protein levels in five patients with infantile and juvenile disease. J Mol Med (Berl). 2009 Jan;87(1):31-41. doi: 10.1007/s00109-008-0402-7. Epub 2008, Sep 18. PMID:18802676 doi:10.1007/s00109-008-0402-7
↑ Guenther UP, Handoko L, Laggerbauer B, Jablonka S, Chari A, Alzheimer M, Ohmer J, Plottner O, Gehring N, Sickmann A, von Au K, Schuelke M, Fischer U. IGHMBP2 is a ribosome-associated helicase inactive in the neuromuscular disorder distal SMA type 1 (DSMA1). Hum Mol Genet. 2009 Apr 1;18(7):1288-300. doi: 10.1093/hmg/ddp028. Epub 2009 Jan , 20. PMID:19158098 doi:10.1093/hmg/ddp028
↑ de Planell-Saguer M, Schroeder DG, Rodicio MC, Cox GA, Mourelatos Z. Biochemical and genetic evidence for a role of IGHMBP2 in the translational machinery. Hum Mol Genet. 2009 Jun 15;18(12):2115-26. doi: 10.1093/hmg/ddp134. Epub 2009 Mar, 19. PMID:19299493 doi:10.1093/hmg/ddp134
↑ Lim SC, Bowler MW, Lai TF, Song H. The Ighmbp2 helicase structure reveals the molecular basis for disease-causing mutations in DMSA1. Nucleic Acids Res. 2012 Sep 10. PMID:22965130 doi:http://dx.doi.org/10.1093/nar/gks792

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4b3f"

Categories: Human | Lim, S C | Song, H | Helicase | Hydrolase

@@ Line 1: / Line 1: @@
 ==crystal structure of Ighmbp2 helicase==
 <StructureSection load='4b3f' size='340' side='right' caption='[[4b3f]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4b3f]] 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=4B3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B3F FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4b3f]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B3F FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1msz|1msz]], [[4b3g|4b3g]]</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=4b3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b3f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4b3f RCSB], [http://www.ebi.ac.uk/pdbsum/4b3f PDBsum]</span></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=4b3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b3f OCA], [http://pdbe.org/4b3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4b3f RCSB], [http://www.ebi.ac.uk/pdbsum/4b3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4b3f ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4b3f" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Lim, S C]]
 [[Category: Song, H]]
 [[Category: Helicase]]
 [[Category: Hydrolase]]

4b3f

From Proteopedia

Revision as of 14:54, 4 August 2016

crystal structure of Ighmbp2 helicase

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox