1j8c
Solution Structure of the Ubiquitin-like Domain of hPLIC-2Solution Structure of the Ubiquitin-like Domain of hPLIC-2
Structural highlights
DiseaseUBQL2_HUMAN Defects in UBQLN2 are the cause of amyotrophic lateral sclerosis type 15 with or without frontotemporal dementia (ALS15) [MIM:300857. A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS15 may develop frontotemporal dementia.[1] [2] [3] [4] FunctionUBQL2_HUMAN Increases the half-life of proteins destined to be degraded by the proteasome; may modulate proteasome-mediated protein degradation.[5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 26S proteasome is essential for the proteolysis of proteins that have been covalently modified by the attachment of polyubiquitinated chains. Although the 20S core particle performs the degradation, the 19S regulatory cap complex is responsible for recognition of polyubiquitinated substrates. We have focused on how the S5a component of the 19S complex interacts with different ubiquitin-like (ubl) modules, to advance our understanding of how polyubiquitinated proteins are targeted to the proteasome. To achieve this, we have determined the solution structure of the ubl domain of hPLIC-2 and obtained a structural model of hHR23a by using NMR spectroscopy and homology modeling. We have also compared the S5a binding properties of ubiquitin, SUMO-1, and the ubl domains of hPLIC-2 and hHR23a and have identified the residues on their respective S5a contact surfaces. We provide evidence that the S5a-binding surface on the ubl domain of hPLIC-2 is required for its interaction with the proteasome. This study provides structural insights into protein recognition by the proteasome, and illustrates how the protein surface of a commonly utilized fold has highly evolved for various biological roles. Structural studies of the interaction between ubiquitin family proteins and proteasome subunit S5a.,Walters KJ, Kleijnen MF, Goh AM, Wagner G, Howley PM Biochemistry. 2002 Feb 12;41(6):1767-77. PMID:11827521[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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