Protein interface remodeling in a chemically induced protein dimer

Brian R. White, Jonathan C.T. Carlson, Jessie L. Kerns, Carston R Wagner

Research output: Contribution to journalArticle

Abstract

Although the development of chemically induced, self-assembled protein-based materials is rapidly expanding, methods for directing their assembly in solution are sparse, and problems of population heterogeneity remain. By exerting control over the assembly of advanced protein structures, new classes of ordered protein nanomaterials become feasible, affecting numerous applications ranging from therapeutics to nanostructural engineering. Focusing on a protein-based method for modulating the stability of a chemically induced dihydrofolate reductase (DHFR) dimer, we demonstrate the sensitivity of a methotrexate competition assay in determining the change in DHFR-DHFR binding cooperativity via interfacial mutations over a 1.3 kcal/mol range. This represents a change of more than 40% of the dimer complex binding energy conferred from protein-protein cooperativity (~3.1 kcal/mol). With the development of this investigative system and refinement of protein-based techniques for complex stability modulation, the directed assembly of protein nanomaterials into heterocomplexes and a concomitant decrease in population heterogeneity becomes a realizable goal.

Original languageEnglish (US)
Pages (from-to)393-403
Number of pages11
JournalJournal of Molecular Recognition
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2012

Fingerprint

Tetrahydrofolate Dehydrogenase
Proteins
Nanostructures
Population Characteristics
Methotrexate
Mutation
Therapeutics

Keywords

  • DHFR
  • chemically induced dimerization
  • competition
  • dimerizer
  • methotrexate
  • nanostructures
  • protein interface
  • self-assembly

Cite this

Protein interface remodeling in a chemically induced protein dimer. / White, Brian R.; Carlson, Jonathan C.T.; Kerns, Jessie L.; Wagner, Carston R.

In: Journal of Molecular Recognition, Vol. 25, No. 7, 01.07.2012, p. 393-403.

Research output: Contribution to journalArticle

White, Brian R. ; Carlson, Jonathan C.T. ; Kerns, Jessie L. ; Wagner, Carston R. / Protein interface remodeling in a chemically induced protein dimer. In: Journal of Molecular Recognition. 2012 ; Vol. 25, No. 7. pp. 393-403.
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