Kelch proteins (and Kelch-like
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s) are a widespread group of proteins that contain multiple
Kelch motifs. The kelch domain generally occurs as a set of five to seven kelch
tandem repeats that form a
β-propeller 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 ...
. Kelch-repeat β-propellers are generally involved in protein–protein interactions, though the large diversity of domain architectures and limited sequence identity between kelch motifs make characterisation of the kelch superfamily difficult.
Structure
The
N-terminus
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
of several Kelch proteins contain other protein domains, including
Discoidin,
F-box, and
Broad-complex, Tramtrack, Bric-a-Brac/Poxvirus Zinc finger (BTB/POZ) domains. Kelch proteins may also only have a β-propeller architecture. The BTB domain of kelch proteins (if present) allows the formation of homo- or
heterodimer
In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...
s that mediate
protein–protein interaction
Protein–protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and t ...
s.
The
C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein
Proteins are large biomolecules and macromolecules that comp ...
of Kelch proteins contains kelch repeats. Each kelch repeat is a sequence of 44–55
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 in length, usually occurring in clusters of 4 – 7 repeats.
Each kelch repeat forms a "blade" of the β-propeller fold, consisting of a four-stranded antiparallel
β-sheet
The beta sheet (β-sheet, also β-pleated sheet) is a common structural motif, motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone chain, backbon ...
secondary structure
Protein secondary structure is the local spatial conformation of the polypeptide backbone excluding the side chains. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
, arranged radially around a central axis, packed onto its adjoining repeats via hydrophobic contacts.
Kelch-repeat β-propellers undergo a variety of binding interactions with other proteins, notably the
actin filaments
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 p ...
of a cell.
Function
Kelch-like proteins are known to act as substrate adaptors for
Cullin 3 ubiquitin ligases.
Organisms
The first Kelch protein (from which this family derives its name) was isolated from ''
Drosophila
''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...
'', in which Kelch-mutant females lay sterile, cup-shaped eggs;
UNDERSTANDING THE FUNCTION OF ACTIN-BINDING PROTEINS THROUGH GENETIC ANALYSIS OF ''DROSOPHILA'' OOGENESIS
by Andrew M. Hudson and Lynn Cooley; in the Annual Review of Genetics
The ''Annual Review of Genetics'' is an annual peer-reviewed scientific review journal published by Annual Reviews. It was established in 1967 and covers all topics related to the genetics of viruses, bacteria, fungi, plants, and animals, includi ...
, Vol. 36: 455–488 (Volume publication date December 2002); retrieved 12 December 2013 The word ' is German for 'chalice, cup'. Kelch proteins have also been isolated in many other animals, plants, bacteria, fungi, and even virus (restricted to Poxviridae
''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. The family contains 22 genera that are assigned to two subfamilies: ''Chordopoxvirinae'' and ''Entomopoxvirinae''. ''Entomopoxvirinae'' ...
).
Human proteins containing Kelch motifs
ATRN
Attractin is a protein that in humans is encoded by the ''ATRN'' gene.
Attractin is a Group XI C-type lectin
A C-type lectin (CLEC) is a type of carbohydrate-binding protein known as a lectin. The C-type designation is from their requirement ...
; ATRNL1; CCIN; ENC1; FBXO42;
GAN; HCFC1; HCFC2; IPP; IVNS1ABP; KBTBD10; KBTBD11; KBTBD2;
KBTBD3; KBTBD4; KBTBD5; KBTBD6; KBTBD7; KBTBD8; KEAP1;
KIAA1900; KLHDC1; KLHDC2; KLHDC3; KLHDC4; KLHDC5; KLHDC6; KLHDC7A; KLHDC7B;
KLHDC8A; KLHDC8B; KLHDC9; KLHDC10; KLHL1; KLHL10; KLHL11; KLHL12; KLHL13;
KLHL14; KLHL15; KLHL17; KLHL18; KLHL2; KLHL20; KLHL21; KLHL22;
KLHL23; KLHL24; KLHL25; KLHL26; KLHL28; KLHL29; KLHL3; KLHL30;
KLHL31; KLHL32; KLHL34; KLHL4; KLHL40; KLHL5; KLHL6; KLHL7; KLHL8;
KLHL9; LZTR1; MEGF8; MKLN1; RABEPK; SARCOSIN;
References
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{{Protein tandem repeats