7FH1

Structure of the human Meckelin

Summary for 7FH1

• Entry DOI: 10.2210/pdb7fh1/pdb
• EMDB information: 31584
• Descriptor: Meckelin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: cryo-em, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 234328.93

Authors

Gong, D.S. (deposition date: 2021-07-29, release date: 2021-12-01)

Primary citation

Liu, D.,Qian, D.,Shen, H.,Gong, D.
Structure of the human Meckel-Gruber protein Meckelin.
Sci Adv, 7:eabj9748-eabj9748, 2021

PubMed Abstract: 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.

PubMed: 34731008
DOI: 10.1126/sciadv.abj9748

Experimental method

ELECTRON MICROSCOPY (3.34 Å)