WH1 domains, also known as EVH1 domains, are evolutionary conserved

protein domains In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of se ...

found on WASP (VASP) proteins, which are often involved in actin polymerization.

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.

Structure

Tertiary structure Protein tertiary structure is the three-dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains and the ...

of the WH1 domain of the

Mena The Middle East and North Africa (MENA), also referred to as West Asia and North Africa (WANA) or South West Asia and North Africa (SWANA), is a geographic region which comprises the Middle East (also called West Asia) and North Africa together ...

protein revealed

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

similarities with the

pleckstrin Pleckstrins are a family of proteins found in platelets and other cells. The name derives from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. The prototype protein, now called pleckstrin-1, was first identified in ...

(PH) domain. The overall fold consists of a compact parallel beta-sandwich, closed along one edge by a long

alpha helix An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the Protein secondary structure, secondary structure of proteins. It is al ...

. A highly conserved cluster of three surface-exposed aromatic side-chains forms the recognition site for the molecule's target

ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...

Interactions

The WASP protein family control actin polymerization by activating the Arp2/3 complex. WASP is defective in

Wiskott–Aldrich syndrome Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). It is also sometimes called the e ...

(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. 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. 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.

EVH1

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 In molecular biology, a protein domain is a region of a protein's Peptide, polypeptide chain that is self-stabilizing and that Protein folding, folds independently from the rest. Each domain forms a compact folded Protein tertiary structure, thre ...

. EVH1 domains recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues. The EVH1 domain is found in multi-domain

Ena/Vasp homology proteins ENA/VASP homology proteins or EVH proteins are a family of closely related proteins involved in cell motility in vertebrate and invertebrate animals. EVH proteins are modular proteins that are involved in actin polymerization, as well as interact ...

implicated in a diverse range of signalling,

nuclear transport Nuclear transport refers to the mechanisms by which molecules move across the nuclear membrane of a cell. The entry and exit of large molecules from the cell nucleus is tightly controlled by the nuclear pore complexes (NPCs). Although small molecule ...

and

cytoskeletal The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all Cell (biology), cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane ...

events. This domain of around 115

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s is present in species ranging from

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

s. Many EVH1-containing proteins associate with actin-based

s and play a role in

organisation. EVH1 domains recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues.;

Examples

Human genes encoding proteins containing the WH1 (EVH1) domain include: * ENAH, EVL *

HOMER1 Homer protein homolog 1 or Homer1 is a neuronal protein that in humans is encoded by the ''HOMER1'' gene. Other names are Vesl and PSD-Zip45. Structure Homer1 protein has an N-terminal EVH1 domain, involved in protein interaction, and a C-ter ...

HOMER2 Homer protein homolog 2 is a protein that in humans is encoded by the ''HOMER2'' gene. This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function. The en ...

HOMER3 Homer protein homolog 3 is a protein that in humans is encoded by the ''HOMER3'' gene. Function This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor fun ...

SPRED1 Sprouty-related, EVH1 domain-containing protein 1 (pronounced ''spread-1'') is a protein that in humans is encoded by the ''SPRED1'' gene located on chromosome 15q13.2 and has seven coding exons. Function SPRED-1 is a member of the Sprouty fa ...

SPRED2 Sprouty-related, EVH1 domain-containing protein 2 is a protein that in humans is encoded by the ''SPRED2'' gene. Function SPRED2 is a member of the Sprouty (see SPRY1)/SPRED family of proteins that regulate growth factor-induced activation of ...

SPRED3 Sprouty-related, EVH1 domain-containing protein 3 also known as Spread-3 is a protein that in humans is encoded by the ''SPRED3'' gene. Spread-3 is a member of the Sprouty (see SPRY1/SPRED) family of proteins that regulate growth factor A gr ...

VASP Viação Aérea São Paulo S/A (São Paulo Airways), better known as VASP, was an airline with its head office in the VASP Building on the grounds of São Paulo–Congonhas Airport in São Paulo, Brazil. It had main bases at São Paulo's two m ...

, WAS, WASL

References

External links

* * * {{InterPro content, IPR007875 Protein domains