Proteins get tough

The unfolding of a mechanically weaker protein domain can be inhibited by inserting it into a stronger domain, creating the possibility of forming multifunctional elastomeric proteins.

Credit: © 2009 ACS

Elastomeric proteins are used in biology to give structural support and withstand applied mechanical force. Most natural elastomeric proteins are made up of individually folded separate domains and under mechanical force the weakest domain will unfold first, with the rest following in order of mechanical stability. This generates a problem when incorporating protein domains with other non-elastomeric functions into elastomeric proteins to create artificial multifunctional proteins. The incorporated proteins tend to be weaker and unfold under mechanical strain, thus losing their functionality.

Now Qing Peng and Hongbin Li at the University of British Columbia, Canada, have succeeded in incorporating¹ a mechanically weaker lysozyme domain (T4L) into a stronger domain (GL5) resulting in the protection of T4L from mechanical loads. They created a hybrid protein in which T4L was inserted within the amino acid sequence of GL5 without major disruption to the structures of either protein.

The mechanical strength of the hybrid protein was determined using single-molecule atomic force microscopy — a technique that can apply small forces over short distances and monitor unfolding events. The researchers saw that T4L does not unfold until after GL5 unfolds, even though the reverse would usually be expected. The protein can also be thought of as a mechanically controlled enzyme switch that could be switched off by applying force.