Structure of the human Meckel-Gruber protein Meckelin

Mutations in the Meckelin 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-A 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. 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.

Automated summary

A study reported the structural characteristics of human Meckelin, including a unique protein folding pattern and a stable homodimer structure, providing a basis for further exploration of the function and disease mechanisms of Meckelin.