5XQH

Crystal structure of truncated human Rogdi

Summary for 5XQH

• Entry DOI: 10.2210/pdb5xqh/pdb
• Descriptor: Protein rogdi homolog (2 entities in total)
• Functional Keywords: rogdi, kohlschutter-tonz syndrome, cell cycle
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus envelope : Q9GZN7
• Total number of polymer chains: 1
• Total formula weight: 30328.03

Authors

Lee, H.,Lee, C. (deposition date: 2017-06-07, release date: 2017-07-12, Last modification date: 2024-10-16)

Primary citation

Lee, H.,Jeong, H.,Choe, J.,Jun, Y.,Lim, C.,Lee, C.
The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tonz Syndrome
Sci Rep, 7:3972-3972, 2017

PubMed Abstract: Kohlschutter-Tönz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. Rogdi, an essential protein, is highly conserved across metazoans, and mutations in Rogdi are linked to KTS. However, how certain mutations in Rogdi abolish its physiological functions and cause KTS is not known. In this study, we determined the crystal structure of human Rogdi protein at atomic resolution. Rogdi forms a novel elongated curved structure comprising the α domain, a leucine-zipper-like four-helix bundle, and a characteristic β-sheet domain. Within the α domain, the N-terminal H1 helix (residues 19-45) pairs with the C-terminal H6 helix (residues 252-287) in an antiparallel manner, indicating that the integrity of the four-helix bundle requires both N- and C-terminal residues. The crystal structure, in conjunction with biochemical data, indicates that the α domain might undergo a conformational change and provide a structural platform for protein-protein interactions. Disruption of the four-helix bundle by mutation results in significant destabilization of the structure. This study provides structural insights into how certain mutations in Rogdi affect its structure and cause KTS, which has important implications for the development of pharmaceutical agents against this debilitating neurological disease.

PubMed: 28638151
DOI: 10.1038/s41598-017-04120-x

Experimental method

X-RAY DIFFRACTION (2.04 Å)