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

Journal article

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.

Authors: Rosenzweig, B; Ross, N; Adler, M; Hamilton, A

• Publication status: Published
• Journal: Journal of the American Chemical Society
• Volume: 132
• Issue: 19
• Pages: 6749-6754
• Publication date: 2010-05-01
• DOI: 10.1021/ja100485n
• EISSN: 1520-5126
• ISSN: 0002-7863
• Language: English
• Keywords: Protein Multimerization; Thermodynamics; Protein Binding; Protein Structure, Quaternary; C-Reactive Protein; Oligodeoxyribonucleotides; Phosphorylcholine; Metals, Alkali