Villin-1

Last updated
Villin-1
Identifiers
SymbolVIL1
Alt. symbolsVIL
NCBI gene 7429
HGNC 12690
OMIM 193040
RefSeq NM_007127
UniProt P09327
Other data
Locus Chr. 2 q35-q36
villin 2 (ezrin)
Identifiers
SymbolVIL2
NCBI gene 7430
HGNC 12691
OMIM 123900
RefSeq NM_003379
UniProt P15311
Other data
Locus Chr. 6 q22-q27
The helix bundle in the headpiece domain of chicken villin. Villin-1qqv.png
The helix bundle in the headpiece domain of chicken villin.

Villin-1 is a 92.5 kDa tissue-specific actin-binding protein associated with the actin core bundle of the brush border. [1] Villin-1 is encoded by the VIL1 gene. Villin-1 contains multiple gelsolin-like domains capped by a small (8.5 kDa) "headpiece" at the C-terminus consisting of a fast and independently folding three-helix bundle that is stabilized by hydrophobic interactions. [2] The headpiece domain is a commonly studied protein in molecular dynamics due to its small size and fast folding kinetics and short primary sequence. [3] [4]

Contents

Structure

Villin-1 is made up of seven domains, six homologous domains make up the N-terminal core and the remaining domain makes up the C-terminal cap. [3] Villin contains three phosphatidylinositol 4,5-biphosphate (PIP2) binding sites, one of which is located at the head piece and the other two in the core. [5] The core domain is approximately 150 amino acid residues grouped in six repeats. On this core is an 87 residue, hydrophobic, C-terminal headpiece [1] The headpiece (HP67) is made up of a compact, 70 amino acid folded protein at the C-terminus. This headpiece contains an F-actin binding domain. Residues K38, E39, K65, 70-73:KKEK, G74, L75 and F76 surround a hydrophobic core and are believed to be involved in the binding of F-actin to villin-1. Residues E39 and K70 form a salt bridge buried within the headpiece which serves to connect N and C terminals. This salt bridge may also orient and fix the C-terminal residues involved in F-actin binding as in the absence of this salt bridge no binding occurs. A hydrophobic “cap” is formed by residue W64 side chains, which is completely conserved throughout the villin family. Below this cap is a crown of alternative positive and negative charged localities. [5] Villin can undergo post-translational modifications like tyrosine phosphorylation. [6] Villin-1 has the ability to dimerize and the dimerization site is located at the amino end of the protein. [7]

Expression

Villin-1 is an actin binding protein expressed mainly in the brush border of the epithelium in vertebrates but sometimes it is ubiquitously expressed in protists and plants. [4] Villin is found localized in the microvilli of the brush border of the epithelium lining of the gut and renal tubules in vertebrates. [5]

Function

Villin-1 is believed to function in the bundling, nucleation, capping and severing of actin filaments. [1] In vertebrates, villin proteins help to support the microfilaments of the microvilli of the brush border. However, knockout mice appear to show ultra-structurally normal microvilli reminding us that the function of villin is not definitively known; it may play a role in cell plasticity through F-actin severing. [5] The six-repeat villin core is responsible for Ca2+ actin severing while the headpiece is responsible for actin crosslinking and bundling (Ca independent). Villin is postulated to be the controlling protein for Ca2+ induced actin severing in the brush border. Ca2+ inhibits proteolytic cleavage of the domains of the 6 N-terminal core which inhibits actin severing. [3] In normal mice raising Ca2+ levels induces the severing of actin by villin, whereas in villin knockout mice this activity does not occur in response to heightened Ca2+ levels. [8] In the presence of low concentrations of Ca2+ the villin headpiece functions to bundle actin filaments whereas in the presence of high Ca2+ concentrations the N-terminal caps and severs these filaments. [1] The association of PIP2 with villin inhibits the actin capping and severing action and increases actin binding at the headpiece region, possibly through structural changes in the protein. PIP2 increases actin bundling not only by decreasing the severing action of villin but also through dissociating capping proteins, releasing actin monomers from sequestering proteins and stimulating actin nucleation and cross linking. [3]

Villin subdomain

The C-terminal subdomain of Villin Headpiece VHP67, denoted VHP35, is stabilised in part, by a buried cluster of three phenylalanine residues. Its small size and high helical content are expected to promote rapid folding, and this has been confirmed experimentally. Villin-4 C-terminal construct VHP76 in Arabidopsis thaliana has been shown to exhibit higher affinity for F-actin in increasing concentrations of Ca2+, which further confirms the function of villin.

Structure

It has a simple topology consisting of three α-helices that form a well-packed hydrophobic core.

Degradation and regulation

Currently, it is theorized the regulation of plant villins are caused by degradation via the binding protein auxin, which targets the headpiece domain (VHP).

See also

Related Research Articles

Microvillus Microscopic protrusion of a cell membrane that increases surface area substantially

Microvilli are microscopic cellular membrane protrusions that increase the surface area for diffusion and minimize any increase in volume, and are involved in a wide variety of functions, including absorption, secretion, cellular adhesion, and mechanotransduction.

Vinculin

In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton. Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane.

Leucine zipper DNA-binding structural motif

A leucine zipper is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amino acid segment and the display of these amino acid sequences on an idealized alpha helix revealed a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns. The polypeptide segments containing these periodic arrays of leucine residues were proposed to exist in an alpha-helical conformation and the leucine side chains from one alpha helix interdigitate with those from the alpha helix of a second polypeptide, facilitating dimerization.

Actin-binding proteins are proteins that bind to actin. This may mean ability to bind actin monomers, or polymers, or both.

ADF/Cofilin family

ADF/cofilin is a family of actin-binding proteins associated with the rapid depolymerization of actin microfilaments that give actin its characteristic dynamic instability. This dynamic instability is central to actin's role in muscle contraction, cell motility and transcription regulation.

Major sperm protein

Major sperm protein (MSP) is a nematode specific small protein of 126 amino acids with a molecular weight of 14 kDa. It is the key player in the motility machinery of nematodes that propels the crawling movement/motility of nematode sperm. It is the most abundant protein present in nematode sperm, comprising 15% of the total protein and more than 40% of the soluble protein. MSP is exclusively synthesized in spermatocytes of the nematodes. The MSP has two main functions in the reproduction of the helminthes: i) as cytosolic component it is responsible for the crawling movement of the mature sperm, and ii) once released, it acts as hormone on the female germ cells, where it triggers oocyte maturation and stimulates the oviduct wall to contract to bring the oocytes into position for fertilization. MSP has first been identified in Caenorhabditis elegans.

Gelsolin (cellular) Mammalian protein found in Homo sapiens

Gelsolin is an actin-binding protein that is a key regulator of actin filament assembly and disassembly. Gelsolin is one of the most potent members of the actin-severing gelsolin/villin superfamily, as it severs with nearly 100% efficiency.

A helix bundle is a small protein fold composed of several alpha helices that are usually nearly parallel or antiparallel to each other.

Talin is a high-molecular-weight cytoskeletal protein concentrated at regions of cell–substratum contact and, in lymphocytes, at cell–cell contacts. Discovered in 1983 by Keith Burridge and colleagues, talin is a ubiquitous cytosolic protein that is found in high concentrations in focal adhesions. It is capable of linking integrins to the actin cytoskeleton either directly or indirectly by interacting with vinculin and α-actinin.

Ezrin Protein-coding gene in the species Homo sapiens

Ezrin also known as cytovillin or villin-2 is a protein that in humans is encoded by the EZR gene.

Capping protein (actin filament) muscle Z-line, alpha 1 Protein-coding gene in the species Homo sapiens

F-actin-capping protein subunit alpha-1 is a protein that in humans is encoded by the CAPZA1 gene.

Macrophage-capping protein

Macrophage-capping protein (CAPG) also known as actin regulatory protein CAP-G is a protein that in humans is encoded by the CAPG gene.

Unconventional myosin-Ia

Unconventional myosin-Ia is a protein that in humans is encoded by the MYO1A gene.

SVIL

Supervillin is a protein that in humans is encoded by the SVIL gene.

SCIN

Scinderin is a protein that in humans is encoded by the SCIN gene. Scinderin is an actin severing protein belonging to the gelsolin superfamily. It was discovered in Dr. Trifaro's laboratory at the University of Ottawa, Canada. Secretory tissues are rich in scinderin. In these tissues scinderin, a calcium dependent protein, regulates cortical actin networks. Normally secretory vesicles are excluded from release sites on the plasma membrane by the presence of a cortical actin filament network. During cell stimulation, calcium channels open allowing calcium ions to enter the secretory cell. Increase in intracellular calcium activates scinderin with the consequent actin filament severing and local dissociation of actin filament networks. This allows the movement of secretory vesicles to release sites on the plasma membrane.

Coronin is an actin binding protein which also interacts with microtubules and in some cell types is associated with phagocytosis. Coronin proteins are expressed in a large number of eukaryotic organisms from yeast to humans.

ERM protein family Protein family

The ERM protein family consists of three closely related proteins, ezrin, radixin and moesin. The three paralogs, ezrin, radixin and moesin, are present in vertebrates, whereas other species have only one ERM gene. Therefore, in vertebrates these paralogs likely arose by gene duplication.

Actin assembly-inducing protein

The Actin assembly-inducing protein (ActA) is a protein encoded and used by Listeria monocytogenes to propel itself through a mammalian host cell. ActA is a bacterial surface protein comprising a membrane-spanning region. In a mammalian cell the bacterial ActA interacts with the Arp2/3 complex and actin monomers to induce actin polymerization on the bacterial surface generating an actin comet tail. The gene encoding ActA is named actA or prtB.

Plasma gelsolin

Plasma gelsolin (pGSN) is an 83 kDa abundant protein constituent of normal plasma and an important component of the innate immune system. The identification of pGSN in Drosophila melanogaster and C. elegans points to an ancient origin early in evolution. Its extraordinary structural conservation reflects its critical regulatory role in multiple essential functions. Its roles include the breakdown of filamentous actin released from dead cells, activation of macrophages, and localization of the inflammatory response. Substantial decreases in plasma levels are observed in acute and chronic infection and injury in both animal models and in humans. Supplementation therapies with recombinant human pGSN have been shown effective in more than 20 animal models.

Villin 1

Villin 1 is a protein that in humans is encoded by the VIL1 gene.

References

  1. 1 2 3 4 Friederich E, Vancompernolle K, Louvard D, Vandekerckhove J (September 1999). "Villin function in the organization of the actin cytoskeleton. Correlation of in vivo effects to its biochemical activities in vitro". The Journal of Biological Chemistry. 274 (38): 26751–60. doi: 10.1074/jbc.274.38.26751 . PMID   10480879.
  2. ↑ Ghoshdastider U, Popp D, Burtnick LD, Robinson RC (November 2013). "The expanding superfamily of gelsolin homology domain proteins". Cytoskeleton. 70 (11): 775–95. doi:10.1002/cm.21149. PMID   24155256. S2CID   205643538.
  3. 1 2 3 4 Bazari WL, Matsudaira P, Wallek M, Smeal T, Jakes R, Ahmed Y (July 1988). "Villin sequence and peptide map identify six homologous domains". Proceedings of the National Academy of Sciences of the United States of America. 85 (14): 4986–90. Bibcode:1988PNAS...85.4986B. doi: 10.1073/pnas.85.14.4986 . PMC   281672 . PMID   2839826.
  4. 1 2 Klahre U, Friederich E, Kost B, Louvard D, Chua NH (January 2000). "Villin-like actin-binding proteins are expressed ubiquitously in Arabidopsis". Plant Physiology. 122 (1): 35–48. doi:10.1104/pp.122.1.35. PMC   58842 . PMID   10631247.
  5. 1 2 3 4 Meng J, Vardar D, Wang Y, Guo HC, Head JF, McKnight CJ (September 2005). "High-resolution crystal structures of villin headpiece and mutants with reduced F-actin binding activity". Biochemistry. 44 (36): 11963–73. doi:10.1021/bi050850x. PMID   16142894.
  6. ↑ Panebra A, Ma SX, Zhai LW, Wang XT, Rhee SG, Khurana S (September 2001). "Regulation of phospholipase C-gamma(1) by the actin-regulatory protein villin". American Journal of Physiology. Cell Physiology. 281 (3): C1046-58. doi:10.1152/ajpcell.2001.281.3.C1046. PMID   11502583.
  7. ↑ George SP, Wang Y, Mathew S, Srinivasan K, Khurana S (September 2007). "Dimerization and actin-bundling properties of villin and its role in the assembly of epithelial cell brush borders". The Journal of Biological Chemistry. 282 (36): 26528–41. doi: 10.1074/jbc.M703617200 . PMID   17606613.
  8. ↑ Revenu C, Courtois M, Michelot A, Sykes C, Louvard D, Robine S (2007). "Villin severing activity enhances actin-based motility in vivo". Molecular Biology of the Cell. 18 (3): 827–38. doi:10.1091/mbc.E06-05-0423. PMC   1805090 . PMID   17182858.

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