Roles of histidine 31 and tryptophan 34 in the structure, self-association, and folding of murine interleukin-6

Biochemistry
J M MatthewsR J Simpson

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine which is involved in a broad spectrum of activities such as immune defense, hematopoiesis, and the acute phase response, as well as in the pathogenesis of multiple myeloma. A series of murine IL-6 (mIL-6) mutants, H31A, W34A, and H31A/W34A, were constructed to investigate the roles of His31 and Trp34 in the structure, conformational stability, time-dependent aggregation, folding, and spectral properties of mIL-6. The characteristic pH-dependent quenching of fluorescence of mIL-6 at low pH was shown to be caused by an interaction between Trp34 and protonated His31 at low pH and not associated with Trp157. Denaturant-induced equilibrium unfolding experiments monitored by fluorescence and far-UV CD showed that the increased quantum yield and blue shift of the wavelength of the emission maximum observed for mIL-6 at moderate denaturant concentrations were also associated with Trp34, rather than Trp157. The tendency to form aggregation-prone unfolding intermediates, as judged by poor fits to a two-state unfolding mechanism, low m values (slopes of the unfolding curve in the transition region), and the range of denaturant concentrations over which these intermediates formed, was show...Continue Reading

References

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Citations

May 1, 1997·Protein Science : a Publication of the Protein Society·R J SimpsonL D Ward
Jun 24, 2003·Biochimica Et Biophysica Acta·Rita MeurisseAnnick Thomas
Sep 8, 2005·Journal of the American Chemical Society·Madhuri ChattopadhyayGlenn L Millhauser
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·B S KendrickT W Randolph
Dec 20, 2003·Hybridoma and Hybridomics·Stephen HamiltonJörg-M Kupsch
Sep 2, 1998·Journal of Pharmaceutical Sciences·B S KendrickJ F Carpenter
Mar 30, 2004·Proteins·Mazdak KhajehpourJane M Vanderkooi
Nov 8, 2005·Biotechnology and Bioengineering·Diana Fedunová, Marián Antalík
May 4, 2011·Developmental Neurobiology·Petrina A GeorgalaDavid J Price
Mar 31, 2018·International Journal of Molecular Sciences·Yang YangMauno Vihinen

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