6zmm
From Proteopedia
Crystal structure of human NDRG1
Structural highlights
DiseaseNDRG1_HUMAN Charcot-Marie-Tooth disease type 4D. The disease is caused by variants affecting the gene represented in this entry. FunctionNDRG1_HUMAN Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase activation and apoptosis. Has a role in cell trafficking, notably of the Schwann cell, and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy.[1] [2] [3] [4] Publication Abstract from PubMedN-myc downstream regulated gene 1 (NDRG1) is a tumour suppressor involved in vesicular trafficking and stress response. NDRG1 participates in peripheral nerve myelination, and mutations in the NDRG1 gene lead to Charcot-Marie-Tooth neuropathy. The 43-kDa NDRG1 is considered as an inactive member of the alpha/beta hydrolase superfamily. In addition to a central alpha/beta hydrolase fold domain, NDRG1 consists of a short N terminus and a C-terminal region with three 10-residue repeats. We determined the crystal structure of the alpha/beta hydrolase domain of human NDRG1 and characterised the structure and dynamics of full-length NDRG1. The structure of the alpha/beta hydrolase domain resembles the canonical alpha/beta hydrolase fold with a central beta sheet surrounded by alpha helices. Small-angle X-ray scattering and CD spectroscopy indicated a variable conformation for the N- and C-terminal regions. NDRG1 binds to various types of lipid vesicles, and the conformation of the C-terminal region is modulated upon lipid interaction. Intriguingly, NDRG1 interacts with metal ions, such as nickel, but is prone to aggregation in their presence. Our results uncover the structural and dynamic features of NDRG1, as well as elucidate its interactions with metals and lipids, and encourage studies to identify a putative hydrolase activity of NDRG1. Crystal and solution structure of NDRG1, a membrane-binding protein linked to myelination and tumour suppression.,Mustonen V, Muruganandam G, Loris R, Kursula P, Ruskamo S FEBS J. 2020 Dec 10. doi: 10.1111/febs.15660. PMID:33305529[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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