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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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PDB id:
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| Name: |
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Signaling protein
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Title:
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Crystal structure of the ternary rgmb-bmp2-neo1 complex
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Structure:
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Neogenin. Chain: a. Fragment: 5th and 6th fn type 3 like domains. Engineered: yes. Other_details: chain c and chain d is the result of an autocatalytic cleavage between residues asp168 and pro169. Bone morphogenetic protein 2, bmp2. Chain: b. Fragment: c-terminal domain signaling domain.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta plyss.
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Resolution:
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3.15Å
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R-factor:
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0.198
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R-free:
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0.236
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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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Key ref:
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E.G.Healey
et al.
(2015).
Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein.
Nat Struct Biol,
22,
458-465.
PubMed id:
DOI:
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Date:
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27-Mar-15
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Release date:
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06-May-15
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PROCHECK
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Headers
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References
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Q92859
(NEO1_HUMAN) -
Neogenin from Homo sapiens
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Seq:
Struc:
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1461 a.a.
201 a.a.*
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P12643
(BMP2_HUMAN) -
Bone morphogenetic protein 2 from Homo sapiens
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Seq:
Struc:
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396 a.a.
104 a.a.
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DOI no:
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Nat Struct Biol
22:458-465
(2015)
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PubMed id:
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Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein.
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E.G.Healey,
B.Bishop,
J.Elegheert,
C.H.Bell,
S.Padilla-Parra,
C.Siebold.
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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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