3vf0 | pdb_00003vf0
Raver1 in complex with metavinculin L954 deletion mutant
Structural highlights
DiseaseVINC_HUMAN Defects in VCL are the cause of cardiomyopathy dilated type 1W (CMD1W) [MIM:611407. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.[1] [2] Defects in VCL are the cause of familial hypertrophic cardiomyopathy type 15 (CMH15) [MIM:613255. It is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.[3] FunctionVINC_HUMAN Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion.[4] Publication Abstract from PubMedVinculin is a key regulator of the actin cytoskeleton attachment to the cell membrane at cellular adhesion sites, which is crucial for processes such as cell motility and migration, development, survival, and wound healing. Vinculin loss results in embryonic lethality, cardiovascular diseases, and cancer. Its tail domain, Vt, is crucial for vinculin activation and focal adhesion turnover and binds to the actin cytoskeleton and acidic phospholipids upon which it unfurls. The RNA binding protein raver1 regulates the assembly of focal adhesions transcriptionally by binding to vinculin. The muscle-specific splice form, metavinculin, is characterized by a 68-residue insert in the tail domain (MVt) and correlates with hereditary idiopathic dilated cardiomyopathy. Here, we report that metavinculin can bind to raver1 in its inactive state. Our crystal structure explains this permissivity, where an extended coil unique to MVt is unfurled in the MVtDelta954:raver1 complex structure. Our binding assays show that raver1 forms a ternary complex with MVt and vinculin mRNA. These findings suggest that the metavinculin:raver1:RNA complex is constitutively recruited to adhesion complexes. The Metavinculin Tail Domain Directs Constitutive Interactions with Raver1 and vinculin RNA.,Lee JH, Rangarajan ES, Vonrhein C, Bricogne G, Izard T J Mol Biol. 2012 Jun 15. PMID:22709580[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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