Structure of the human CLC-7/Ostm1 complex reveals a novel state |
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| Authors: | Zhixuan Zhang Long Chen Jin He Ji She |
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| Affiliation: | School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China |
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| Abstract: | CLC-7 functions as a Cl?/H+ exchanger in lysosomes. Defects in CLC-7 and its β-subunit, Ostm1, result in osteopetrosis and neurodegeneration. Here, we present the cryogenic electron microscopy (cryo-EM) structure of the human CLC-7/Ostm1 complex (HsCLC-7/Ostm1) at a resolution of 3.6 ?. Our structure reveals a new state of the CLC-7/Ostm1 heterotetramer, in which the cytoplasmic domain of CLC-7 is absent, likely due to high flexibility. The disordered cytoplasmic domain is probably not able to restrain CLC-7 subunits and thus allow their relative movements. The movements result in an approximately half smaller interface between the CLC-7 transmembrane domains than that in a previously reported CLC-7/Ostm1 structure with a well-folded cytoplasmic domain. Key interactions involving multiple osteopetrosis-related residues are affected by the interface change. |
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| Keywords: | CLC-7 Ostm1 osteopetrosis chloride transporter single-particle cryo-EM |
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