HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The metavinculin tail domain directs constitutive interactions with raver1 and vinculin RNA.

Abstract
Vinculin 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 MVtΔ954: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.
AuthorsJun Hyuck Lee, Erumbi S Rangarajan, Clemens Vonrhein, Gerard Bricogne, Tina Izard
JournalJournal of molecular biology (J Mol Biol) Vol. 422 Issue 5 Pg. 697-704 (Oct 05 2012) ISSN: 1089-8638 [Electronic] Netherlands
PMID22709580 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Ltd. All rights reserved.
Chemical References
  • Carrier Proteins
  • Nuclear Proteins
  • RAVER1 protein, human
  • Ribonucleoproteins
  • metavinculin
  • Vinculin
  • RNA
Topics
  • Carrier Proteins (chemistry, metabolism)
  • Crystallography, X-Ray
  • Models, Molecular
  • Nuclear Proteins (chemistry, metabolism)
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • RNA (chemistry, metabolism)
  • Ribonucleoproteins
  • Vinculin (chemistry, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: