We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

5dcp

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:31, 6 December 2017

Crystal structure of the human filamin B Ig-like domains 16-17

Structural highlights

5dcp is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	FLNB, FLN1L, FLN3, TABP, TAP (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FLNB_HUMAN] Note=Interaction with FLNA may compensate for dysfunctional FLNA homodimer in the periventricular nodular heterotopia (PVNH) disorder. Defects in FLNB are the cause of atelosteogenesis type 1 (AO1) [MIM:108720]; also known as giant cell chondrodysplasia or spondylohumerofemoral hypoplasia. Atelosteogenesis are lethal short-limb skeletal dysplasias with vertebral abnormalities, disharmonious skeletal maturation, poorly modeled long bones and joint dislocations.^[1] Defects in FLNB are the cause of atelosteogenesis type 3 (AO3) [MIM:108721]. Atelosteogenesis are short-limb lethal skeletal dysplasias with vertebral abnormalities, disharmonious skeletal maturation, poorly modeled long bones and joint dislocations. In AO3 recurrent respiratory insufficiency and/or infections usually result in early death.^[2] Defects in FLNB are the cause of boomerang dysplasia (BOOMD) [MIM:112310]. This is a perinatal lethal osteochondrodysplasia characterized by absence or underossification of the limb bones and vertebre. Boomerang dysplasia is distinguished from atelosteogenesis on the basis of a more severe defect in mineralisation, with complete absence of ossification in some limb elements and vertebral segments.^[3] Defects in FLNB are the cause of Larsen syndrome (LRS) [MIM:150250]. An osteochondrodysplasia characterized by large-joint dislocations and characteristic craniofacial abnormalities. The cardinal features of the condition are dislocations of the hip, knee and elbow joints, with equinovarus or equinovalgus foot deformities. Spatula-shaped fingers, most marked in the thumb, are also present. Craniofacial anomalies include hypertelorism, prominence of the forehead, a depressed nasal bridge, and a flattened midface. Cleft palate and short stature are often associated features. Spinal anomalies include scoliosis and cervical kyphosis. Hearing loss is a well-recognized complication.^[4] ^[5] Defects in FLNB are the cause of spondylocarpotarsal synostosis syndrome (SCT) [MIM:272460]; also known as spondylocarpotarsal syndrome (SCT) or congenital synspondylism or vertebral fusion with carpal coalition or congenital scoliosis with unilateral unsegmented bar. The disorder is characterized by short stature and vertebral, carpal and tarsal fusions.^[6]

Function

[FLNB_HUMAN] Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro.

Publication Abstract from PubMed

Cells' ability to sense mechanical cues in their environment is crucial for fundamental cellular processes, leading defects in mechanosensing to be linked to many diseases. The actin cross-linking protein Filamin has an important role in the conversion of mechanical forces into biochemical signals. Here, we reveal how mutations in Filamin genes known to cause Larsen syndrome and Frontometaphyseal dysplasia can affect the structure and therefore function of Filamin domains 16 and 17. Employing X-ray crystallography, the structure of these domains was first solved for the human Filamin B. The interaction seen between domains 16 and 17 is broken by shear force as revealed by steered molecular dynamics simulations. The effects of skeletal dysplasia associated mutations of the structure and mechanosensing properties of Filamin were studied by combining various experimental and theoretical techniques. The results showed that Larsen syndrome associated mutations destabilize or even unfold domain 17. Interestingly, those Filamin functions that are mediated via domain 17 interactions with other proteins are not necessarily affected as strongly interacting peptide binding to mutated domain 17 induces at least partial domain folding. Mutation associated to Frontometaphyseal dysplasia, in turn, transforms 16-17 fragment from compact to an elongated form destroying the force-regulated domain pair.

Skeletal Dysplasia Mutations Effect on Human Filamins' Structure and Mechanosensing.,Seppala J, Bernardi RC, Haataja TJK, Hellman M, Pentikainen OT, Schulten K, Permi P, Ylanne J, Pentikainen U Sci Rep. 2017 Jun 26;7(1):4218. doi: 10.1038/s41598-017-04441-x. PMID:28652603^[7]

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

References

↑ Krakow D, Robertson SP, King LM, Morgan T, Sebald ET, Bertolotto C, Wachsmann-Hogiu S, Acuna D, Shapiro SS, Takafuta T, Aftimos S, Kim CA, Firth H, Steiner CE, Cormier-Daire V, Superti-Furga A, Bonafe L, Graham JM Jr, Grix A, Bacino CA, Allanson J, Bialer MG, Lachman RS, Rimoin DL, Cohn DH. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat Genet. 2004 Apr;36(4):405-10. Epub 2004 Feb 29. PMID:14991055 doi:10.1038/ng1319
↑ Krakow D, Robertson SP, King LM, Morgan T, Sebald ET, Bertolotto C, Wachsmann-Hogiu S, Acuna D, Shapiro SS, Takafuta T, Aftimos S, Kim CA, Firth H, Steiner CE, Cormier-Daire V, Superti-Furga A, Bonafe L, Graham JM Jr, Grix A, Bacino CA, Allanson J, Bialer MG, Lachman RS, Rimoin DL, Cohn DH. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat Genet. 2004 Apr;36(4):405-10. Epub 2004 Feb 29. PMID:14991055 doi:10.1038/ng1319
↑ Bicknell LS, Morgan T, Bonafe L, Wessels MW, Bialer MG, Willems PJ, Cohn DH, Krakow D, Robertson SP. Mutations in FLNB cause boomerang dysplasia. J Med Genet. 2005 Jul;42(7):e43. PMID:15994868 doi:10.1136/jmg.2004.029967
↑ Krakow D, Robertson SP, King LM, Morgan T, Sebald ET, Bertolotto C, Wachsmann-Hogiu S, Acuna D, Shapiro SS, Takafuta T, Aftimos S, Kim CA, Firth H, Steiner CE, Cormier-Daire V, Superti-Furga A, Bonafe L, Graham JM Jr, Grix A, Bacino CA, Allanson J, Bialer MG, Lachman RS, Rimoin DL, Cohn DH. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat Genet. 2004 Apr;36(4):405-10. Epub 2004 Feb 29. PMID:14991055 doi:10.1038/ng1319
↑ Bicknell LS, Farrington-Rock C, Shafeghati Y, Rump P, Alanay Y, Alembik Y, Al-Madani N, Firth H, Karimi-Nejad MH, Kim CA, Leask K, Maisenbacher M, Moran E, Pappas JG, Prontera P, de Ravel T, Fryns JP, Sweeney E, Fryer A, Unger S, Wilson LC, Lachman RS, Rimoin DL, Cohn DH, Krakow D, Robertson SP. A molecular and clinical study of Larsen syndrome caused by mutations in FLNB. J Med Genet. 2007 Feb;44(2):89-98. Epub 2006 Jun 26. PMID:16801345 doi:10.1136/jmg.2006.043687
↑ Krakow D, Robertson SP, King LM, Morgan T, Sebald ET, Bertolotto C, Wachsmann-Hogiu S, Acuna D, Shapiro SS, Takafuta T, Aftimos S, Kim CA, Firth H, Steiner CE, Cormier-Daire V, Superti-Furga A, Bonafe L, Graham JM Jr, Grix A, Bacino CA, Allanson J, Bialer MG, Lachman RS, Rimoin DL, Cohn DH. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat Genet. 2004 Apr;36(4):405-10. Epub 2004 Feb 29. PMID:14991055 doi:10.1038/ng1319
↑ Seppala J, Bernardi RC, Haataja TJK, Hellman M, Pentikainen OT, Schulten K, Permi P, Ylanne J, Pentikainen U. Skeletal Dysplasia Mutations Effect on Human Filamins' Structure and Mechanosensing. Sci Rep. 2017 Jun 26;7(1):4218. doi: 10.1038/s41598-017-04441-x. PMID:28652603 doi:http://dx.doi.org/10.1038/s41598-017-04441-x

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/5dcp"

@@ Line 3: / Line 3: @@
 <StructureSection load='5dcp' size='340' side='right' caption='[[5dcp]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5dcp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DCP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5dcp]] 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=5DCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DCP FirstGlance]. <br>
-</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=5dcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dcp OCA], [http://pdbe.org/5dcp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dcp RCSB], [http://www.ebi.ac.uk/pdbsum/5dcp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dcp ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FLNB, FLN1L, FLN3, TABP, TAP ([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=5dcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dcp OCA], [http://pdbe.org/5dcp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dcp RCSB], [http://www.ebi.ac.uk/pdbsum/5dcp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dcp ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 10: / Line 11: @@
 == Function ==
 [[http://www.uniprot.org/uniprot/FLNB_HUMAN FLNB_HUMAN]] Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cells' ability to sense mechanical cues in their environment is crucial for fundamental cellular processes, leading defects in mechanosensing to be linked to many diseases. The actin cross-linking protein Filamin has an important role in the conversion of mechanical forces into biochemical signals. Here, we reveal how mutations in Filamin genes known to cause Larsen syndrome and Frontometaphyseal dysplasia can affect the structure and therefore function of Filamin domains 16 and 17. Employing X-ray crystallography, the structure of these domains was first solved for the human Filamin B. The interaction seen between domains 16 and 17 is broken by shear force as revealed by steered molecular dynamics simulations. The effects of skeletal dysplasia associated mutations of the structure and mechanosensing properties of Filamin were studied by combining various experimental and theoretical techniques. The results showed that Larsen syndrome associated mutations destabilize or even unfold domain 17. Interestingly, those Filamin functions that are mediated via domain 17 interactions with other proteins are not necessarily affected as strongly interacting peptide binding to mutated domain 17 induces at least partial domain folding. Mutation associated to Frontometaphyseal dysplasia, in turn, transforms 16-17 fragment from compact to an elongated form destroying the force-regulated domain pair.
+Skeletal Dysplasia Mutations Effect on Human Filamins' Structure and Mechanosensing.,Seppala J, Bernardi RC, Haataja TJK, Hellman M, Pentikainen OT, Schulten K, Permi P, Ylanne J, Pentikainen U Sci Rep. 2017 Jun 26;7(1):4218. doi: 10.1038/s41598-017-04441-x. PMID:28652603<ref>PMID:28652603</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 5dcp" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Pentikainen, U]]
 [[Category: Seppala, J]]

5dcp

From Proteopedia

Revision as of 07:31, 6 December 2017

Crystal structure of the human filamin B Ig-like domains 16-17

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox