The Rubicon homology domain (also known as RH domain) is an evolutionarily conserved protein domain of approximately 250 amino acids that mediates protein–protein interaction.[1] RH domains are present in several human proteins involved in regulation of autophagy and endosomal trafficking.[2] While not all RH domains have been characterized, those of human Rubicon and PLEKHM1 mediate interaction with the small GTPase Rab7, which is found on late endosomes and autophagosomes.[2][3]
RH domains contain 16 conserved cysteine and histidine residues that bind zinc atoms and form at least 4 zinc finger motifs.[2][3] Amino acid residues toward the C-terminus of the RH domain of Rubicon have been shown to be essential for interaction with Rab7.[2]
Structure
The 3D atomic structure of the Rubicon RH domain in complex with Rab7 has been determined by X-ray crystallography.[2] The structure of the RH domain has an "L" shape, with the base of the "L" making contact with the switch regions of Rab7.[2] The structure is predominantly alpha helical, with short beta strand regions present in the vicinity of zinc finger motifs.[2] The N-terminal region of the Rubicon RH domain resembles a FYVE domain, however the basic residues required for canonical FYVE domain binding of PI3P are not present.[2]
Proteins containing an RH domain
RH domains are found in a number of proteins, including (in humans):
- Rubicon, the defining member of the RH domain-containing family of proteins and a negative regulator of autophagy[4]
- PLEKHM1, a protein implicated in osteopetrosis
- Pacer, a positive regulator of autophagy
- DEF8, a regulator of lysosome peripheral distribution[5]
- PLEKHM3, involved in skeletal muscle differentiation[6]
References
- ^ "Pfam: Family: zf-RING_9 (PF13901)". pfam.xfam.org. Retrieved 2022-05-31.
- ^ a b c d e f g h Bhargava HK, Tabata K, Byck JM, Hamasaki M, Farrell DP, Anishchenko I, et al. (July 2020). "Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex". Proceedings of the National Academy of Sciences of the United States of America. 117 (29): 17003–17010. doi:10.1073/pnas.2008030117. PMC 7382272. PMID 32632011.
- ^ a b Tabata K, Matsunaga K, Sakane A, Sasaki T, Noda T, Yoshimori T (December 2010). "Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain". Molecular Biology of the Cell. 21 (23): 4162–4172. doi:10.1091/mbc.E10-06-0495. PMC 2993745. PMID 20943950.
- ^ "RUBCN - Run domain Beclin-1-interacting and cysteine-rich domain-containing protein - Homo sapiens (Human) - RUBCN gene & protein". www.uniprot.org. Retrieved 2022-05-31.
- ^ "Def8 - Differentially expressed in FDCP 8 - Mus musculus (Mouse) - Def8 gene & protein". www.uniprot.org. Retrieved 2022-05-31.
- ^ "PLEKHM3 - Pleckstrin homology domain-containing family M member 3 - Homo sapiens (Human) - PLEKHM3 gene & protein". www.uniprot.org. Retrieved 2022-05-31.
This page was last edited on 3 January 2023, at 18:44