The Rubicon homology domain (also known as RH domain) is an evolutionarily 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 o ...

of approximately 250 amino acids that mediates protein–protein interaction. RH domains are present in several human proteins involved in regulation of

autophagy Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...

and endosomal trafficking. While not all RH domains have been characterized, those of human

Rubicon The Rubicon ( la, Rubico; it, Rubicone ; rgn, Rubicôn ) is a shallow river in northeastern Italy, just north of Rimini. It was known as Fiumicino until 1933, when it was identified with the ancient river Rubicon, famously crossed by Julius C ...

and PLEKHM1 mediate interaction with the small GTPase Rab7, which is found on late endosomes and autophagosomes. RH domains contain 16 conserved

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, s ...

and

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the ...

residues that bind zinc atoms and form at least 4 zinc finger motifs. Amino acid residues toward the C-terminus of the RH domain of Rubicon have been shown to be essential for interaction with Rab7.

Structure

The 3D atomic structure of the Rubicon RH domain in complex with Rab7 has been determined by

X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angle ...

. The structure of the RH domain has an "L" shape, with the base of the "L" making contact with the switch regions of Rab7. The structure is predominantly

alpha helical 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 earli ...

, with short

beta strand The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

regions present in the vicinity of zinc finger motifs. The N-terminal region of the Rubicon RH domain resembles a

FYVE domain In molecular biology the FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1 (yeast orthologue of PIKfyve), YOTB, Vac 1 (vesicle transport protein), and EEA1, in which it has been found. FYVE domains bind phosphatidyli ...

, however the basic residues required for canonical FYVE domain binding of

PI3P Phosphatidylinositol 3-phosphate (PtdIns3''P'') is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and II ...

are not present.

Proteins containing an RH domain

RH domains are found in a number of proteins, including (in humans): *

, the defining member of the RH domain-containing family of proteins and a negative regulator of autophagy * PLEKHM1, a protein implicated in

osteopetrosis Osteopetrosis, literally "stone bone", also known as marble bone disease or Albers-Schönberg disease, is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, ...

* Pacer, a positive regulator of autophagy * DEF8, a regulator of lysosome peripheral distribution *

PLEKHM3 Pleckstrin Homology domain containing Family M Member 3, or PLEKHM3, is the hypothetical protein that in humans is encoded by the ''PLEKHM3'' gene.: plekstrin homology domain containing family member 3 PLEKHM3 is also known as DAPR (differentiatio ...

, involved in skeletal muscle differentiation

References

{{reflist Protein domains Protein structure