Cryo-EM structure of human lysosomal cobalamin exporter ABCD4
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Dear Editor,Cobalamin,also known as vitamin B12,can only be biosynthesized by certain bacteria and archaea.As an essential nutrient for humans,it should be obtained from daily food.1 Exogenous cobalamin is taken up by the cell through an endocytosis process,then released into the lysosome as a free form,and finally pumped out to the cytosol for utilization.2 The human ATP-binding cassette (ABC) transporter ABCD4 localized on lysosomal membrane is indispensable for the efflux of cobalamin from lysosome to cytosol.3 Mutations in ABCD4 gene may result in cobalamin deficiency and inborn diseases.The patients suffer from combined symptoms:hypotonia,lethargy,poor feeding,bone marrow suppression,macrocytic anemia,and heart defects.3 However,the absence of the structure of human ABCD4 limits our understanding of the molecular mechanism of pathogenesis.
molecular mechanism
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We thank Prof.Nieng Yan at Princeton University for help with establishment of our membrane protein research platform.We thank Xiaojun Huang and Boling Zhu at the Center for Biological Imaging,Core Facilities for Protein Science at the Institute of Biophysics,Chinese Academy of Sciences for technica2015CB910103;the Chinese Academy of ScienceXDB08020304;the National Natural Science Foundation of China31621002;the Fundamental Research Funds for the Central UniversitiesWK2070000117