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

Version 1

      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://