Lawrence A Potempa - Cell membranes and liposomes dissociate C-reactive protein (CRP) to form a new, biologically active structural intermediate: mCRPm

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  Publication Details (including relevant citation   information):

    FASEB J. 21, 284–294   (2007)

  Abstract:

  Emerging   evidence indicates that C-reactive

  protein   (CRP) has at least two conformationally

  distinct   isoforms,

    i.e.

  , pentameric   CRP (pCRP) and

  monomeric   CRP (mCRP or CRP subunit). Both CRP

  isoforms are   proposed to play roles in inflammation

  and may   participate in the pathogenesis of cardiovascular

  disease.   However, the origin of mCRP

    in situ

  and

  the   interplay between the two CRP isoforms under

  physiological/pathological   circumstances remain elusive.

  Herein, by   probing conformational alteration,

  neoepitope   expression, and direct visualization using

  electron-microscopy,   we have shown that calcium-dependent

  binding of   pCRP to membranes, including

  liposomes   and cell membranes, led to a rapid but

  partial   structural change, producing molecules that

  express CRP   subunit antigenicity but with retained

  native   pentameric conformation. This hybrid molecule

  is herein   termed mCRP

  m.   The formation of mCRP

  m

  was   associated with significantly enhanced complement

  fixation.   mCRP

  m

  can further   detach from membrane to

  form the   well-recognized mCRP isoform converted in

  solution   (mCRP

  s

  ) and exert   potent stimulatory effects

  on   endothelial cells. The membrane-induced pCRP

  dissociation   not only provides a physiologically relevant

  scenario for   mCRP formation but may represent an

  important   mechanism for regulating CRP function.—

  Shang-Rong   Ji, Yi Wu, Li Zhu, Lawrence A. Potempa,

  Fen-Ling   Sheng, Wei Lu, and Jing Zhao. Cell membranes

  and   liposomes dissociate C-reactive protein

  (CRP) to   form a new, biologically active structural

  intermediate:   mCRPm.

  Address (URL): http://

 

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