Search results for "filamiini"
showing 10 items of 12 documents
Non-syndromic Mitral Valve Dysplasia Mutation Changes the Force Resilience and Interaction of Human Filamin A
2018
International audience; Filamin A (FLNa), expressed in endocardial endothelia during fetal valve morphogenesis, is key in cardiac development. Missense mutations in FLNa cause non-syndromic mitral valve dysplasia (FLNA-MVD). Here, we aimed to reveal the currently unknown underlying molecular mechanism behind FLNA-MVD caused by the FLNa P637Q mutation. The solved crystal structure of the FLNa3-5 P637Q revealed that this mutation causes only minor structural changes close to mutation site. These changes were observed to significantly affect FLNa's ability to transmit cellular force and to interact with its binding partner. The performed steered molecular dynamics simulations showed that signi…
Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.
2015
Filamins (FLNs) are large, multidomain actin cross-linking proteins with diverse functions. Besides regulating the actin cytoskeleton, they serve as important links between the extracellular matrix and the cytoskeleton by binding cell surface receptors, functioning as scaffolds for signaling proteins, and binding several other cytoskeletal proteins that regulate cell adhesion dynamics. Structurally, FLNs are formed of an amino terminal actin-binding domain followed by 24 immunoglobulin-like domains (IgFLNs). Recent studies have demonstrated that myosin-mediated contractile forces can reveal hidden protein binding sites in the domain pairs IgFLNa18-19 and 20-21, enabling FLNs to transduce me…
Critical Structural Defects Explain Filamin A Mutations Causing Mitral Valve Dysplasia
2019
Mitral valve diseases affect approximately 3% of the population and are the most common reasons for valvular surgery because no drug-based treatments exist. Inheritable genetic mutations have now been established as the cause of mitral valve insufficiency, and four different missense mutations in the filamin A gene (FLNA) have been found in patients suffering from non-syndromic mitral valve dysplasia (MVD). The FLNA protein is expressed, in particular, in endocardial endothelia during fetal valve morphogenesis and is key in cardiac development. The FLNA-MVD causing mutations are clustered in the N-terminal region of FLNA. How the mutations in FLNA modify its structure and function, have mos…
Filamiinin ja pernan tyrosiinikinaasin sitoutuminen sekä vuorovaikutuksen merkitys verihiutaleiden signaloinnissa
2013
Hyytymän muodostuminen tapahtuu verisuoneen kohdistuneen vaurion seurauksena verenvuodon tyrehdyttämiseksi. Hyytymä voi muodostua myös verisuonen pinnalle silloinkin kun verenvuotoa ei esiinny. Irrotessaan verenvuodon mukaan hyytymä voi olla hengenvaarallinen. Erilaiset hyytymän muodostamat veritulpat ovat merkittävä kuolinsyy vuosittain. Verihiutaleet ovat keskeinen tekijä tässä tapahtumassa. Niiden aktivaatio tapahtuu kalvoreseptoreiden ja solun sisäisen signaloinnin monimutkaisesta vuorovaikutuksesta. Tämän tutkimuksen kohteina ovat pernan tyrosiinikinaasi ja filamiini A, joiden välinen vuorovaikutus on tärkeää verihiutaleiden toiminnalle. Verihiutaleet, joissa tämä vuorovaikutus on häir…
Structures, interactions and packing of filamin domains
2011
Filamiini A:n domeenien 16-21 vuorovaikutus dopamiinireseptorin kanssa
2009
Molecular Basis of Filamin A-FilGAP Interaction and Its Impairment in Congenital Disorders Associated with Filamin A Mutations
2009
Background: Mutations in filamin A (FLNa), an essential cytoskeletal protein with multiple binding partners, cause developmental anomalies in humans. Methodology/Principal Findings: We determined the structure of the 23rd Ig repeat of FLNa (IgFLNa23) that interacts with FilGAP, a Rac-specific GTPase-activating protein and regulator of cell polarity and movement, and the effect of the three disease-related mutations on this interaction. A combination of NMR structural analysis and in silico modeling revealed the structural interface details between the C and D b-strands of the IgFLNa23 and the C-terminal 32 residues of FilGAP. Mutagenesis of the predicted key interface residues confirmed the…