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PDBsum entry 2kqn
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Immune system
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PDB id
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2kqn
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References listed in PDB file
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Key reference
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Title
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A single mutation promotes amyloidogenicity through a highly promiscuous dimer interface.
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Authors
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F.C.Peterson,
E.M.Baden,
B.A.Owen,
B.F.Volkman,
M.Ramirez-Alvarado.
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Ref.
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Structure, 2010,
18,
563-570.
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PubMed id
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Abstract
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Light chain amyloidosis is a devastating protein misfolding disease
characterized by the accumulation of amyloid fibrils that causes tissue damage
and organ failure. These fibrils are composed of monoclonal light chain protein
secreted from an abnormal proliferation of bone marrow plasma cells. We
previously reported that amyloidogenic light chain protein AL-09 adopts an
altered dimer while its germline protein (kappaI O18/O8) forms a canonical dimer
observed in other light chain crystal structures. In solution, conformational
heterogeneity obscures all NMR signals at the AL-09 and kappaI O18/O8 dimer
interfaces, so we solved the nuclear magnetic resonance structure of two related
mutants. AL-09 H87Y adopts the normal dimer interface, but the kappaI Y87H
solution structure presents an altered interface rotated 180 degrees relative to
the canonical dimer interface and 90 degrees from the AL-09 arrangement. Our
results suggest that promiscuity in the light chain dimer interface may promote
new intermolecular contacts that may contribute to amyloid fibril structure.
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