The structural and functional analysis of copper transporting P-type ATPase in inborn error of copper metabolism

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1.The intracellular localization of Menkes disease gene (ATP-7A) protein and Wilson disease gene (ATP-7B) proteinBoth of the proteins synthesized from ATP-7A and 7B were localized in the trans-Golgi network under steady conditions. An increase in the intracellular copper concentration resulted in the rapid movement of these proteins to a cytoplasmic vesicular compartment. This copper-specific cellular redistribution of ATP-7A and 7B protein is a reversible process that occurs independent of new protein (small vesicles of copper transport).2.The corelationship between genotype and clinical features in Wilson diseaseThe most of mutations of ATP-7B in hepatic type (including fulminant type) of Wilson disease were one point dilutions that make frame shift. Truncated proteins must be synthesized from these mutated genes. And these proteins may have no any function as a Copper transporter. The patients who have neurologic symptom revealed missense mutation and exon skipping. These mutated protein can be leave some part of function. These results suggest that difference of phenotypes of Wilson disease depend on functional levels of Wilson disease protein. And protein function is regulated by types of gene mutations (genotype). The sever impairment of ATP-7B,such one base deletion would remove function, leads to sever liver dysfunction, such as fulminant type of Wilson disease.