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PDBsum entry 3o8e
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Cell adhesion/immune system
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PDB id
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3o8e
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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 extracellular portion of cd46 provides insights into its interactions with complement proteins and pathogens.
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Authors
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B.D.Persson,
N.B.Schmitz,
C.Santiago,
G.Zocher,
M.Larvie,
U.Scheu,
J.M.Casasnovas,
T.Stehle.
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Ref.
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Plos Pathog, 2010,
6,
e1001122.
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PubMed id
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Abstract
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The human membrane cofactor protein (MCP, CD46) is a central component of the
innate immune system. CD46 protects autologous cells from complement attack by
binding to complement proteins C3b and C4b and serving as a cofactor for their
cleavage. Recent data show that CD46 also plays a role in mediating acquired
immune responses, and in triggering autophagy. In addition to these physiologic
functions, a significant number of pathogens, including select adenoviruses,
measles virus, human herpes virus 6 (HHV-6), Streptococci, and Neisseria, use
CD46 as a cell attachment receptor. We have determined the crystal structure of
the extracellular region of CD46 in complex with the human adenovirus type 11
fiber knob. Extracellular CD46 comprises four short consensus repeats
(SCR1-SCR4) that form an elongated structure resembling a hockey stick, with a
long shaft and a short blade. Domains SCR1, SCR2 and SCR3 are arranged in a
nearly linear fashion. Unexpectedly, however, the structure reveals a profound
bend between domains SCR3 and SCR4, which has implications for the interactions
with ligands as well as the orientation of the protein at the cell surface. This
bend can be attributed to an insertion of five hydrophobic residues in a SCR3
surface loop. Residues in this loop have been implicated in interactions with
complement, indicating that the bend participates in binding to C3b and C4b. The
structure provides an accurate framework for mapping all known ligand binding
sites onto the surface of CD46, thereby advancing an understanding of how CD46
acts as a receptor for pathogens and physiologic ligands of the immune system.
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