WH1 domain

Last updated
WH1 domain
Identifiers
SymbolWH1
Pfam PF00568
InterPro IPR000697
SMART WH1
SCOP2 1evh / SCOPe / SUPFAM
CDD cd01205
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

WH1 domains, also known as EVH1 domains, are evolutionary conserved protein domains found on WASP (VASP) proteins, which are often involved in actin polymerization. [1] [2]

Contents

Function

WH1 domains are important for all cellular processes involving actin, this includes cell motility, cell trafficking, cell division and cytokinesis, cell signalling, and the establishment and maintenance of cell junctions and cell shape. [2]

Structure

Tertiary structure of the WH1 domain of the Mena protein revealed structure similarities with the pleckstrin (PH) domain. The overall fold consists of a compact parallel beta-sandwich, closed along one edge by a long alpha helix. A highly conserved cluster of three surface-exposed aromatic side-chains forms the recognition site for the molecule's target ligands. [3]

Interactions

The WASP protein family control actin polymerization by activating the Arp2/3 complex. WASP is defective in Wiskott–Aldrich syndrome (WAS) whereby in most patient cases, the majority of point mutations occur within the N-terminal WH1 domain. The metabotropic glutamate receptors mGluR1alpha and mGluR5 bind a protein called homer, which is a WH1 domain homologue. [4] [5]

WASP family proteins contain an EVH1 (WH1) in their N-terminals which bind proline-rich sequences in the WASP interacting protein. Proteins of the RanBP1 family contain a WH1 domain in their N-terminal region, which seems to bind a different sequence motif present in the C-terminal part of RanGTP protein. [6] [7]

Tertiary structure of the WH1 domain of the Mena protein revealed structure similarities with the pleckstrin homology (PH) domain. The overall fold consists of a compact parallel beta-sandwich, closed along one edge by a long alpha-helix. A highly conserved cluster of three surface-exposed aromatic side-chains forms the recognition site for the molecules target ligands. [3]

EVH1

EVH1
PDB 1mke EBI.jpg
structure of the n-wasp evh1 domain-wip complex
Identifiers
SymbolEVH1
Pfam PF00568
Pfam clan CL0266
InterPro IPR000697
SMART WH1
SCOP2 1evh / SCOPe / SUPFAM
CDD cd00837
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

A subset of WH1 domains has been termed the EVH1 domain bind a polyproline motif. The EVH1 domain (also known as the WH1, RanBP1-WASP, or enabled/VASP homology 1 domain) is also an evolutionary conserved protein domain. EVH1 domains recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues. [5] [8]

The EVH1 domain is found in multi-domain Ena/Vasp homology proteins implicated in a diverse range of signalling, nuclear transport and cytoskeletal events. This domain of around 115 amino acids is present in species ranging from yeast to mammals. Many EVH1-containing proteins associate with actin-based structures and play a role in cytoskeletal organisation. EVH1 domains recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues. [8] [9] [10]

Examples

Human genes encoding proteins containing the WH1 (EVH1) domain include:

Related Research Articles

<span class="mw-page-title-main">SH3 domain</span> Small protein domain found in some kinases and GTPases

The SRC Homology 3 Domain is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src. It has also been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and cdc25. SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, and the Src kinase and many others. The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases, SH3 proteins usually bind far away from the active site. Approximately 300 SH3 domains are found in proteins encoded in the human genome. In addition to that, the SH3 domain was responsible for controlling protein-protein interactions in the signal transduction pathways and regulating the interactions of proteins involved in the cytoplasmic signaling.

<span class="mw-page-title-main">Microfilament</span> Filament in the cytoplasm of eukaryotic cells

Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other proteins in the cell. Microfilaments are usually about 7 nm in diameter and made up of two strands of actin. Microfilament functions include cytokinesis, amoeboid movement, cell motility, changes in cell shape, endocytosis and exocytosis, cell contractility, and mechanical stability. Microfilaments are flexible and relatively strong, resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton tensile forces. In inducing cell motility, one end of the actin filament elongates while the other end contracts, presumably by myosin II molecular motors. Additionally, they function as part of actomyosin-driven contractile molecular motors, wherein the thin filaments serve as tensile platforms for myosin's ATP-dependent pulling action in muscle contraction and pseudopod advancement. Microfilaments have a tough, flexible framework which helps the cell in movement.

<span class="mw-page-title-main">Wiskott–Aldrich syndrome protein</span> Mammalian protein found in humans

The Wiskott–Aldrich syndrome protein (WASp) is a 502-amino acid protein expressed in cells of the hematopoietic system that in humans is encoded by the WAS gene. In the inactive state, WASp exists in an autoinhibited conformation with sequences near its C-terminus binding to a region near its N-terminus. Its activation is dependent upon CDC42 and PIP2 acting to disrupt this interaction, causing the WASp protein to 'open'. This exposes a domain near the WASp C-terminus that binds to and activates the Arp2/3 complex. Activated Arp2/3 nucleates new F-actin.

<span class="mw-page-title-main">PDZ domain</span>

The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to cytoskeletal components. Proteins with these domains help hold together and organize signaling complexes at cellular membranes. These domains play a key role in the formation and function of signal transduction complexes. PDZ domains also play a highly significant role in the anchoring of cell surface receptors to the actin cytoskeleton via mediators like NHERF and ezrin.

<span class="mw-page-title-main">Testin</span> Protein-coding gene in humans

Testin is a protein that in humans is encoded by the TES gene located on chromosome 7. TES is a 47 kDa protein composed of 421 amino acids found at focal adhesions and is thought to have a role in regulation of cell motility. In addition to this, TES functions as a tumour suppressor. The TES gene is located within a fragile region of chromosome 7, and the promoter elements of the TES gene have been shown to be susceptible to methylation – this prevents the expression of the TES protein. TES came to greater prominence towards the end of 2007 as a potential mechanism for its tumour suppressor function was published.

<span class="mw-page-title-main">LIM domain</span> InterPro Domain

LIM domains are protein structural domains, composed of two contiguous zinc fingers, separated by a two-amino acid residue hydrophobic linker. The domain name is an acronym of the three genes in which it was first identified. LIM is a protein interaction domain that is involved in binding to many structurally and functionally diverse partners. The LIM domain appeared in eukaryotes sometime prior to the most recent common ancestor of plants, fungi, amoeba and animals. In animal cells, LIM domain-containing proteins often shuttle between the cell nucleus where they can regulate gene expression, and the cytoplasm where they are usually associated with actin cytoskeletal structures involved in connecting cells together and to the surrounding matrix, such as stress fibers, focal adhesions and adherens junctions.

<span class="mw-page-title-main">Formins</span> Proteins

Formins (formin homology proteins) are a group of proteins that are involved in the polymerization of actin and associate with the fast-growing end (barbed end) of actin filaments. Most formins are Rho-GTPase effector proteins. Formins regulate the actin and microtubule cytoskeleton and are involved in various cellular functions such as cell polarity, cytokinesis, cell migration and SRF transcriptional activity. Formins are multidomain proteins that interact with diverse signalling molecules and cytoskeletal proteins, although some formins have been assigned functions within the nucleus.

<span class="mw-page-title-main">WASF2</span> Mammalian protein found in Homo sapiens

Wiskott–Aldrich syndrome protein family member 2 is a protein that in humans is encoded by the WASF2 gene.

<span class="mw-page-title-main">NCK1</span> Protein-coding gene in the species Homo sapiens

Cytoplasmic protein NCK1 is a protein that in humans is encoded by the NCK1 gene.

<span class="mw-page-title-main">Vasodilator-stimulated phosphoprotein</span> Mammalian protein found in Homo sapiens

Vasodilator-stimulated phosphoprotein is a protein that in humans is encoded by the VASP gene.

<span class="mw-page-title-main">IQGAP1</span>

Ras GTPase-activating-like protein IQGAP1 (IQGAP1) also known as p195 is a ubiquitously expressed protein that in humans is encoded by the IQGAP1 gene. IQGAP1 is a scaffold protein involved in regulating various cellular processes ranging from organization of the actin cytoskeleton, transcription, and cellular adhesion to regulating the cell cycle.

<span class="mw-page-title-main">ENAH (gene)</span> Protein-coding gene in the species Homo sapiens

Protein enabled homolog is a protein that in humans is encoded by the ENAH gene.

<span class="mw-page-title-main">CD2AP</span> Protein

CD2-associated protein is a protein that in humans is encoded by the CD2AP gene.

<span class="mw-page-title-main">WIPF1</span> Protein-coding gene in the species Homo sapiens

WAS/WASL-interacting protein (WIP) is a protein that in humans is encoded by the WIPF1 gene.

<span class="mw-page-title-main">Enah/Vasp-like</span> Protein-coding gene in the species Homo sapiens

Ena/VASP-like protein is a member of the Ena/VASP family of proteins that in humans is encoded by the EVL gene.

<span class="mw-page-title-main">Cordon-bleu protein</span> Protein found in humans

Protein cordon-bleu is a protein that in humans is encoded by the COBL gene.

<span class="mw-page-title-main">WW domain</span>

The WW domain is a modular protein domain that mediates specific interactions with protein ligands. This domain is found in a number of unrelated signaling and structural proteins and may be repeated up to four times in some proteins. Apart from binding preferentially to proteins that are proline-rich, with particular proline-motifs, [AP]-P-P-[AP]-Y, some WW domains bind to phosphoserine- and phosphothreonine-containing motifs.

<span class="mw-page-title-main">Actin assembly-inducing protein</span>

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.

<span class="mw-page-title-main">GYF domain</span>

In molecular biology, the GYF domain is an approximately 60-amino acid protein domain which contains a conserved GP[YF]xxxx[MV]xxWxxx[GN]YF motif. It was identified in the human intracellular protein termed CD2 binding protein 2 (CD2BP2), which binds to a site containing two tandem PPPGHR segments within the cytoplasmic region of CD2. Binding experiments and mutational analyses have demonstrated the critical importance of the GYF tripeptide in ligand binding. A GYF domain is also found in several other eukaryotic proteins of unknown function. It has been proposed that the GYF domain found in these proteins could also be involved in proline-rich sequence recognition. Resolution of the structure of the CD2BP2 GYF domain by NMR spectroscopy revealed a compact domain with a beta-beta-alpha-beta-beta topology, where the single alpha-helix is tilted away from the twisted, anti-parallel beta-sheet. The conserved residues of the GYF domain create a contiguous patch of predominantly hydrophobic nature which forms an integral part of the ligand-binding site. There is limited homology within the C-terminal 20-30 amino acids of various GYF domains, supporting the idea that this part of the domain is structurally but not functionally important.

References

  1. Symons M, Derry JM, Karlak B, Jiang S, Lemahieu V, Mccormick F, Francke U, Abo A (March 1996). "Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization". Cell. 84 (5): 723–34. doi: 10.1016/S0092-8674(00)81050-8 . PMID   8625410. S2CID   17838931.
  2. 1 2 Veltman DM, Insall RH (2010). "WASP family proteins: their evolution and its physiological implications". Mol Biol Cell. 21 (16): 2880–93. doi:10.1091/mbc.E10-04-0372. PMC   2921111 . PMID   20573979.
  3. 1 2 Prehoda KE, Lee DJ, Lim WA (May 1999). "Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly". Cell. 97 (4): 471–80. doi: 10.1016/S0092-8674(00)80757-6 . PMID   10338211. S2CID   17078939.
  4. Ponting CP, Phillips C (1997). "Identification of homer as a homologue of the Wiskott-Aldrich syndrome protein suggests a receptor-binding function for WH1 domains". J. Mol. Med. 75 (11–12): 769–71. doi:10.1007/s001090050166. PMID   9428607. S2CID   39958754.
  5. 1 2 Niebuhr K, Ebel F, Frank R, Reinhard M, Domann E, Carl UD, Walter U, Gertler FB, Wehland J, Chakraborty T (September 1997). "A novel proline-rich motif present in ActA of Listeria monocytogenes and cytoskeletal proteins is the ligand for the EVH1 domain, a protein module present in the Ena/VASP family". EMBO J. 16 (17): 5433–44. doi:10.1093/emboj/16.17.5433. PMC   1170174 . PMID   9312002.
  6. Callebaut I, Cossart P, Dehoux P (December 1998). "EVH1/WH1 domains of VASP and WASP proteins belong to a large family including Ran-binding domains of the RanBP1 family". FEBS Lett. 441 (2): 181–5. doi:10.1016/S0014-5793(98)01541-5. PMID   9883880. S2CID   8527080.
  7. Beddow AL, Richards SA, Orem NR, Macara IG (April 1995). "The Ran/TC4 GTPase-binding domain: identification by expression cloning and characterization of a conserved sequence motif". Proc. Natl. Acad. Sci. U.S.A. 92 (8): 3328–32. doi: 10.1073/pnas.92.8.3328 . PMC   42159 . PMID   7724562.
  8. 1 2 Ball LJ, Jarchau T, Oschkinat H, Walter U (February 2002). "EVH1 domains: structure, function and interactions". FEBS Lett. 513 (1): 45–52. doi: 10.1016/S0014-5793(01)03291-4 . PMID   11911879. S2CID   10368115.
  9. Pawson T. "EVH1 Domain". The Pawson Lab. Retrieved 2011-06-09.
  10. PDB: 1QC6 ; Fedorov AA, Fedorov E, Gertler F, Almo SC (July 1999). "Structure of EVH1, a novel proline-rich ligand-binding module involved in cytoskeletal dynamics and neural function". Nat. Struct. Biol. 6 (7): 661–5. doi:10.1038/10717. PMID   10404224. S2CID   22881412.
This article incorporates text from the public domain Pfam and InterPro: IPR000697
This article incorporates text from the public domain Pfam and InterPro: IPR007875