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PDBsum entry 4bq8
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Cell adhesion
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PDB id
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4bq8
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Contents |
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195 a.a.
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14 a.a.
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161 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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Structure of the repulsive guidance molecule (rgm)-Neogenin signaling hub.
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Authors
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C.H.Bell,
E.Healey,
S.Van erp,
B.Bishop,
C.Tang,
R.J.Gilbert,
A.R.Aricescu,
R.J.Pasterkamp,
C.Siebold.
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Ref.
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Science, 2013,
341,
77-80.
[DOI no: ]
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PubMed id
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Abstract
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Repulsive guidance molecule family members (RGMs) control fundamental and
diverse cellular processes, including motility and adhesion, immune cell
regulation, and systemic iron metabolism. However, it is not known how RGMs
initiate signaling through their common cell-surface receptor, neogenin (NEO1).
Here, we present crystal structures of the NEO1 RGM-binding region and its
complex with human RGMB (also called dragon). The RGMB structure reveals a
previously unknown protein fold and a functionally important autocatalytic
cleavage mechanism and provides a framework to explain numerous disease-linked
mutations in RGMs. In the complex, two RGMB ectodomains conformationally
stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent
manner. We demonstrate that all RGM-NEO1 complexes share this architecture,
which therefore represents the core of multiple signaling pathways.
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