WH1 domain is an evolutionary conserved

protein domain 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 s ...

. Therefore, it has an important function.

Function

WH1 domains are found on WASP proteins, which are often involved in actin polymerization. Hence, WH1 is 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 may int ...

of the WH1 domain of the

Mena MENA, an acronym in the English language, refers to a grouping of countries situated in and around the Middle East and North Africa. It is also known as WANA, SWANA, or NAWA, which alternatively refers to the Middle East as Western Asia (or a ...

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 Pleckstrin is a protein found in platelets. The name derives from platelet and leukocyte C kinase substrate and the KSTR string of amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional grou ...

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

alpha helix The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...

. 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 (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 electro ...

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 eczem ...

(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

. 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 interac ...

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 cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compo ...

events. This domain of around 115

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s is present in species ranging from

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

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

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-te ...

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 *

SPRED1 Sprouty-related, EVH1 domain-containing protein 1 (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 family of proteins ...

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 gro ...

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 Was or WAS may refer to: * ''Was'', a past-tense form of the English copular verb ''to be'' People * David Was (born c. 1952), the stage name of multi-instrumentalist and songwriter David Weiss * Don Was (born 1952), the stage name of bass guita ...

, WASL

References

External links

* * * {{InterPro content, IPR007875 Protein domains