Altered binding of a multimeric protein by changing the self-assembling properties of its substrate

Brooke A. Rosenzweig, Nathan T. Ross, Marc J. Adler, Andrew Hamilton

Research output: Contribution to journalArticle

Abstract

Artificially controlled cell recognition has potentially far-reaching applications in both the understanding and altering of biological function. The event of recognition often involves a multimeric protein binding a cellular membrane. While such an interaction is energetically favorable, it has been surprisingly underexploited in artificial control of recognition. Herein we describe how changing properties of substrate (phosphocholine, PC) self-assembly can affect both binding behavior and substrate affinity to a pentameric recognition protein (C-reactive protein, CRP). PC was modified with a short, self-assembling DNA strand to make the substrate self-assembly sensitive and responsive to ionic environment. A significant shift in CRP binding affinity was observed when substrates were assembled in the presence of Cs+ rather than K+. Furthermore, alteration of the linker length tethering PC to DNA showed trends similar to other multivalent systems. In optimizing these linker lengths, positive cooperativity increased and K d of the substrate assembly to CRP improved roughly 1000-fold. Such experiments both inform our understanding of biological, multivalent interactions in self-assembling systems and present a potential method to exogenously control events in cell recognition.

Original languageEnglish (US)
Pages (from-to)6749-6754
Number of pages6
JournalJournal of the American Chemical Society
Volume132
Issue number19
DOIs
StatePublished - May 19 2010

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Phosphorylcholine
C-Reactive Protein
Proteins
Protein Binding
Substrates
DNA
Self assembly
Protein C
Membranes
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry
  • Chemistry(all)

Cite this

Altered binding of a multimeric protein by changing the self-assembling properties of its substrate. / Rosenzweig, Brooke A.; Ross, Nathan T.; Adler, Marc J.; Hamilton, Andrew.

In: Journal of the American Chemical Society, Vol. 132, No. 19, 19.05.2010, p. 6749-6754.

Research output: Contribution to journalArticle

Rosenzweig, Brooke A. ; Ross, Nathan T. ; Adler, Marc J. ; Hamilton, Andrew. / Altered binding of a multimeric protein by changing the self-assembling properties of its substrate. In: Journal of the American Chemical Society. 2010 ; Vol. 132, No. 19. pp. 6749-6754.
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