Site-directed mutagenesis of the hinge peptide from the hemagglutinin protein: enhancement of the pH-responsive conformational change

Protein Engineering, Design & Selection : PEDS
Monica CasaliMartin L Yarmush

Abstract

Environmentally responsive proteins and peptides are increasingly finding utility in various engineered systems due to their ability to respond to the presentation of external stimuli. A classic example of this behavior is the influenza hemagglutinin (HA) fusion protein. At neutral pH, HA exists in a non-fusogenic state, but upon exposure to low pH, the conformation of the structure changes to expose a fusogenic peptide. During this structural change, massive rearrangements occur in a subunit of HA (HA2). Crystallography data has shown that a loop of 28 amino acids (residues 54-81) undergoes a dramatic transition from a random coil to an alpha-helix. This segment connects to two flanking helical regions (short and long) to form a long, continuous helix. Here, we report the results of site-directed mutagenesis study on LOOP-36 to further understand the mechanism of this important stimulus-responsive peptide. The conformational transition of a bacterially expressed LOOP-36 was found to be less dramatic than has been previously reported. The systematic mutation of glutamate and histidine residues in the peptide to glutamines (glutamine scanning) did not impact the conformational behavior of the peptide, but the substitution of the...Continue Reading

Citations

Aug 28, 2013·Chemical Reviews·Robert O J Weinzierl
Apr 28, 2010·Annual Review of Biomedical Engineering·Scott BantaMark Blenner
Mar 13, 2012·Nanomedicine : Nanotechnology, Biology, and Medicine·Daniel Martinez-FongIvan Navarro-Quiroga
May 21, 2009·Analytical Biochemistry·Karuppiah ChockalingamScott Banta
Mar 27, 2018·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Arup Kumar Pathak
Jun 21, 2014·The Journal of Biological Chemistry·Aleksandar AntanasijevicMichael Caffrey
Jul 18, 2018·Proceedings of the National Academy of Sciences of the United States of America·Xingcheng LinJosé N Onuchic

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