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Publications [#64108] of Harold P. Erickson

Papers Published

  1. Ohashi, Tomoo and Erickson, Harold P., Domain unfolding plays a role in superfibronectin formation, Journal of Biological Chemistry, vol. 280 no. 47 (2005), pp. 39143 - 39151 [jbc.M509082200]
    (last updated on 2007/04/15)

    Abstract:
    Superfibronectin (sFN) is a fibronectin (FN) aggregate that is formed by mixing FN with anastellin, a fragment of the first type III domain of FN. However, the mechanism of this aggregation has not been clear. In this study, we found that anastellin co-precipitated with FN in a ratio of ~ [similar to] :1, anastellin: FN monomer. The primary binding site for anastellin was in the segment III1-S, which bound three molecules of anastellin and was able to form a precipitate without the rest of the FN molecule. Anastellin binding to III3 caused a conformational change in that domain that exposed a cryptic thermolysin-sensitive site. An additional anastellin binds to III11, where it enhances thermolysin digestion of III11. An engineered disulfide bond in III3 inhibited both aggregation and protease digestion, suggesting that the stability of IIIS is a key factor in sFN formation. We propose a three-step model for sFN formation: 1) FN-III domains spontaneously unfold and refold; 2) anastellin binds to an unfolded domain, preventing its refolding and leaving it with exposed hydrophobic surfaces and β-sheet edges; and 3) these exposed elements bind to similar exposed elements on other molecules, leading to aggregation. The model is consistent with our observation that the kinetics of aggregation are first order, with a reaction time of 500-700 s. Similar mechanisms may contribute to the assembly of the native FN matrix. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

    Keywords:
    Monomers;Molecules;Precipitation (chemical);Chemical bonds;Biochemistry;


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