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Lookup NU author(s): Professor Steve Homans
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The population of one or more partially folded states has been proposed as a critical initial step in amyloid formation for several proteins. Here we use equilibrium denaturation measured by 1H-15N NMR to determine the conformational properties of an amyloidogenic intermediate of human 2-microglobulin (2m) formed at low pH. The data show that this amyloid precursor is a noncooperatively stabilized ensemble that retains stable structure in five of the seven -strands that comprise the native fold. The amyloid precursors of 2m and transthyretin have similar properties despite having structurally unrelated native folds. The data offer a rationale as to why these proteins are both amyloidogenic at low pH and suggest that amyloidosis of these and other proteins may involve ordered assembly from a precursor with similar conformational features.
Author(s): McParland VJ, Kalverda AP, Homans SW, Radford SE
Publication type: Article
Publication status: Published
Journal: Nature Structural Biology
ISSN (print): 1545-9993
ISSN (electronic): 1545-9985
Publisher: Nature Publishing Group
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