4mgx

From Proteopedia

(Difference between revisions)

Revision as of 11:16, 21 December 2022

Crystal structure of human filamin C domains 4-5 and GPIB alpha cytoplasmic domain complex

Structural highlights

4mgx is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FLNC_HUMAN Defects in FLNC are the cause of myopathy myofibrillar type 5 (MFM5) [MIM:609524. A neuromuscular disorder, usually with an adult onset, characterized by focal myofibrillar destruction and pathological cytoplasmic protein aggregations, and clinical features of a limb-girdle myopathy.^[1] Defects in FLNC are the cause of myopathy distal type 4 (MPD4) [MIM:614065. MPD4 is a slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non-specific changes with no evidence of rods, necrosis, or inflammation.^[2]

Function

FLNC_HUMAN Muscle-specific filamin, which plays a central role in muscle cells, probably by functioning as a large actin-cross-linking protein. May be involved in reorganizing the actin cytoskeleton in response to signaling events, and may also display structural functions at the Z lines in muscle cells. Critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers.

Publication Abstract from PubMed

Immunoglobulin-like (Ig) domains are a widely expanded superfamily that acts as interaction motifs or as structural spacers in multi-domain proteins. Vertebrate filamins (FLNs), which are multifunctional actin binding proteins, consists of 24 Ig domains. We have recently discovered that in the C-terminal Rod 2 region of FLN, Ig domains interact with each other forming functional domain pairs, where the interaction with signaling and transmembrane proteins is mechanically regulated by weak actomyosin contraction forces. Here, we investigated if there are similar inter-domain interactions around domain 4 in the N-terminal Rod 1 region of FLN. Protein crystal structures revealed a new type of domain organization between domains 3, 4 and 5. In this module, domains 4 and 5 interact rather tightly whereas domain 3 has a partially flexible interface with domain 4. NMR peptide titration experiments showed that within the three domain module, domain 4 is capable for interaction with a peptide derived from platelet glycoprotein Ib. Crystal structure of FLN domains 4 and 5 in complex with the peptide revealed a typical beta sheet augmentation interaction observed for many FLN ligands. Domain 5 was found to stabilize domain 4, and this could provide a mechanism for the regulation of domain 4 interactions.

A Novel Structural Unit in the N-Terminal Region of Filamins.,Sethi R, Seppala J, Tossavainen H, Ylilauri M, Ruskamo S, Pentikainen OT, Pentikainen U, Permi P, Ylanne J J Biol Chem. 2014 Jan 27. PMID:24469451^[3]

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

References

↑ Vorgerd M, van der Ven PF, Bruchertseifer V, Lowe T, Kley RA, Schroder R, Lochmuller H, Himmel M, Koehler K, Furst DO, Huebner A. A mutation in the dimerization domain of filamin c causes a novel type of autosomal dominant myofibrillar myopathy. Am J Hum Genet. 2005 Aug;77(2):297-304. Epub 2005 May 31. PMID:15929027 doi:10.1086/431959
↑ Duff RM, Tay V, Hackman P, Ravenscroft G, McLean C, Kennedy P, Steinbach A, Schoffler W, van der Ven PF, Furst DO, Song J, Djinovic-Carugo K, Penttila S, Raheem O, Reardon K, Malandrini A, Gambelli S, Villanova M, Nowak KJ, Williams DR, Landers JE, Brown RH Jr, Udd B, Laing NG. Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy. Am J Hum Genet. 2011 Jun 10;88(6):729-40. Epub 2011 May 27. PMID:21620354 doi:10.1016/j.ajhg.2011.04.021
↑ Sethi R, Seppala J, Tossavainen H, Ylilauri M, Ruskamo S, Pentikainen OT, Pentikainen U, Permi P, Ylanne J. A Novel Structural Unit in the N-Terminal Region of Filamins. J Biol Chem. 2014 Jan 27. PMID:24469451 doi:http://dx.doi.org/10.1074/jbc.M113.537456

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Homo sapiens | Large Structures | Sethi R | Ylanne J

@@ Line 1: / Line 1: @@
 ==Crystal structure of human filamin C domains 4-5 and GPIB alpha cytoplasmic domain complex==
-<StructureSection load='4mgx' size='340' side='right' caption='[[4mgx]], [[Resolution|resolution]] 3.16&Aring;' scene=''>
+<StructureSection load='4mgx' size='340' side='right'caption='[[4mgx]], [[Resolution|resolution]] 3.16&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4mgx]] is a 2 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=4MGX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MGX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4mgx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MGX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MGX FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3v8o|3v8o]]</td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mgx OCA], [https://pdbe.org/4mgx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mgx RCSB], [https://www.ebi.ac.uk/pdbsum/4mgx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mgx ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FLNC, ABPL, FLN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4mgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mgx OCA], [http://pdbe.org/4mgx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mgx RCSB], [http://www.ebi.ac.uk/pdbsum/4mgx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mgx ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/FLNC_HUMAN FLNC_HUMAN]] Defects in FLNC are the cause of myopathy myofibrillar type 5 (MFM5) [MIM:[http://omim.org/entry/609524 609524]]. A neuromuscular disorder, usually with an adult onset, characterized by focal myofibrillar destruction and pathological cytoplasmic protein aggregations, and clinical features of a limb-girdle myopathy.<ref>PMID:15929027</ref>   Defects in FLNC are the cause of myopathy distal type 4 (MPD4) [MIM:[http://omim.org/entry/614065 614065]]. MPD4 is a slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non-specific changes with no evidence of rods, necrosis, or inflammation.<ref>PMID:21620354</ref>  [[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[http://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref>   Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[http://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref>   Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[http://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref>   Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[http://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</ref>
+[https://www.uniprot.org/uniprot/FLNC_HUMAN FLNC_HUMAN] Defects in FLNC are the cause of myopathy myofibrillar type 5 (MFM5) [MIM:[https://omim.org/entry/609524 609524]. A neuromuscular disorder, usually with an adult onset, characterized by focal myofibrillar destruction and pathological cytoplasmic protein aggregations, and clinical features of a limb-girdle myopathy.<ref>PMID:15929027</ref>   Defects in FLNC are the cause of myopathy distal type 4 (MPD4) [MIM:[https://omim.org/entry/614065 614065]. MPD4 is a slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non-specific changes with no evidence of rods, necrosis, or inflammation.<ref>PMID:21620354</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/FLNC_HUMAN FLNC_HUMAN]] Muscle-specific filamin, which plays a central role in muscle cells, probably by functioning as a large actin-cross-linking protein. May be involved in reorganizing the actin cytoskeleton in response to signaling events, and may also display structural functions at the Z lines in muscle cells. Critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers. [[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.
+[https://www.uniprot.org/uniprot/FLNC_HUMAN FLNC_HUMAN] Muscle-specific filamin, which plays a central role in muscle cells, probably by functioning as a large actin-cross-linking protein. May be involved in reorganizing the actin cytoskeleton in response to signaling events, and may also display structural functions at the Z lines in muscle cells. Critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 21: @@
 ==See Also==
-*[[Filamin|Filamin]]
+*[[Filamin 3D structures|Filamin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Sethi, R]]
+[[Category: Large Structures]]
-[[Category: Ylanne, J]]
+[[Category: Sethi R]]
-[[Category: Immunoglobulin like fold]]
+[[Category: Ylanne J]]
-[[Category: Z-disk]]
-[[Category: Structural protein]]

4mgx

From Proteopedia

Revision as of 11:16, 21 December 2022

Crystal structure of human filamin C domains 4-5 and GPIB alpha cytoplasmic domain complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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