6GJE

Structure of the Amnionless(20-357)-Cubilin(36-135) complex

Summary for 6GJE

• Entry DOI: 10.2210/pdb6gje/pdb
• Descriptor: Protein amnionless, Cubilin (3 entities in total)
• Functional Keywords: receptor, vitamin b12, cubilin, amnionless, amn, cubn, kidney, reabsorption, proximal tubule, protein transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 73323.97

Authors

Larsen, C.,Etzerodt, A.,Madsen, M.,Skjoedt, K.,Moestrup, S.K.,Andersen, C.B.F. (deposition date: 2018-05-16, release date: 2018-12-19, Last modification date: 2024-10-16)

Primary citation

Larsen, C.,Etzerodt, A.,Madsen, M.,Skjodt, K.,Moestrup, S.K.,Andersen, C.B.F.
Structural assembly of the megadalton-sized receptor for intestinal vitamin B12uptake and kidney protein reabsorption.
Nat Commun, 9:5204-5204, 2018

PubMed Abstract: The endocytic receptor cubam formed by the 460-kDa protein cubilin and the 45-kDa transmembrane protein amnionless (AMN), is essential for intestinal vitamin B (B) uptake and for protein (e.g. albumin) reabsorption from the kidney filtrate. Loss of function of any of the two components ultimately leads to serious B deficiency and urinary protein loss in humans (Imerslund-Gräsbeck's syndrome, IGS). Here, we present the crystal structure of AMN in complex with the amino-terminal region of cubilin, revealing a sophisticated assembly of three cubilin subunits combining into a single intertwined β-helix domain that docks to a corresponding three-faced β-helix domain in AMN. This β-helix-β-helix association thereby anchors three ligand-binding cubilin subunits to the transmembrane AMN. Electron microscopy of full-length cubam reveals a 700-800 Å long tree-like structure with the potential of dimerization into an even larger complex. Furthermore, effects of known human mutations causing IGS are explained by the structural information.

PubMed: 30523278
DOI: 10.1038/s41467-018-07468-4

Experimental method

X-RAY DIFFRACTION (2.3 Å)