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PDBsum entry 4ui2
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Signaling protein
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PDB id
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4ui2
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Contents |
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201 a.a.
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104 a.a.
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80 a.a.
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156 a.a.
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References listed in PDB file
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Key reference
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Title
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Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein.
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Authors
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E.G.Healey,
B.Bishop,
J.Elegheert,
C.H.Bell,
S.Padilla-Parra,
C.Siebold.
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Ref.
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Nat Struct Biol, 2015,
22,
458-465.
[DOI no: ]
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PubMed id
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Abstract
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Repulsive guidance molecules (RGMs) control crucial processes including cell
motility, adhesion, immune-cell regulation and systemic iron metabolism. RGMs
signal via the neogenin (NEO1) and the bone morphogenetic protein (BMP)
pathways. Here, we report crystal structures of the N-terminal domains of all
human RGM family members in complex with the BMP ligand BMP2, revealing a new
protein fold and a conserved BMP-binding mode. Our structural and functional
data suggest a pH-linked mechanism for RGM-activated BMP signaling and offer a
rationale for RGM mutations causing juvenile hemochromatosis. We also determined
the crystal structure of the ternary BMP2-RGM-NEO1 complex, which, along with
solution scattering and live-cell super-resolution fluorescence microscopy,
indicates BMP-induced clustering of the RGM-NEO1 complex. Our results show how
RGM acts as the central hub that links BMP and NEO1 and physically connects
these fundamental signaling pathways.
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