Structure of the human Meckel-Gruber protein Meckelin

Mutations in the gene account for most cases of the Meckel-Gruber syndrome, the most severe ciliopathy with a 100% mortality rate. Here, we report a 3.3-Å cryo–electron microscopy structure of human Meckelin (also known as TMEM67 and MKS3). The structure reveals a unique protein fold consisting of a...

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Published inScience advances Vol. 7; no. 45; p. eabj9748
Main Authors Liu, Dongliang, Qian, Dandan, Shen, Huaizong, Gong, Deshun
Format Journal Article
LanguageEnglish
Published United States American Association for the Advancement of Science 05.11.2021
Subjects
Biomedicine and Life Sciences
Life Sciences
Organismal Biology
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Summary:Mutations in the gene account for most cases of the Meckel-Gruber syndrome, the most severe ciliopathy with a 100% mortality rate. Here, we report a 3.3-Å cryo–electron microscopy structure of human Meckelin (also known as TMEM67 and MKS3). The structure reveals a unique protein fold consisting of an unusual cysteine-rich domain that folds as an arch bridge stabilized by 11 pairs of disulfide bonds, a previously uncharacterized domain named β sheet–rich domain, a previously unidentified seven-transmembrane fold wherein TM4 to TM6 are broken near the cytoplasmic surface of the membrane, and a coiled-coil domain placed below the transmembrane domain. Meckelin forms a stable homodimer with an extensive dimer interface. Our structure establishes a framework for dissecting the function and disease mechanisms of Meckelin.
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These authors contributed equally to this work as first authors.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abj9748