W. H. Bragg Lecture 2009

Mechanoenzymatics
Presented by Herman Gaub
Ludwig-Maximilians-Universität München


Wednesday, 28 October 2009 at 16:00
University College London in the Harrie Massey Lecture Theatre


followed by a reception with light refreshments in E7 Physics

Abstract

Biological responses to mechanical stress require strain-sensing molecules, whose mechanically induced conformational changes are relayed to signaling cascades mediating changes in cell and tissue properties.

In muscle, the giant elastic protein titin is implicated in strain sensing via its C-terminal autoinhibited kinase domain (TK) at the sarcomeric M-band. Here, we employ AFM-based single-molecule force spectroscopy to unravel the sequence of conformational changes during force-induced activation of TK. In particular we identify the sub-steps in which the autoinhibition of TK is mechanically relieved at low forces, enabling binding of the co-substrate ATP and thus priming the enzyme for substrate turnover.

Based on this knowledge on the functional mechanisms of the force sensor, we employed protein engineering and designed an artificial force sensor with the goal to report strain via an optical signal. We engineered handles to CalB, a lipase with a fluorescencent product, and investigated the turnover of individual enzymes as a function of the applied force.

About the W.H. Bragg Lecture

In 2004 UCL's Department of Physics and Astronomy decided to establish a series of annual lectures celebrating major advances in condensed matter physics. The series was named after William Henry Bragg, who was the Head of Department from 1915 to 1923. X-ray diffraction analysis of crystal structures began with W. H. Bragg’s instrumentation and insight, and with the availability of synchrotron sources it has developed into an important tool in modern biology.

Venue

To go to  the Harrie Massey Lecture Theatre please enter UCL through the gate adjacent to number 3 Gower Place. Alternatively go to  the back of the UCL Union & Mathematics building on 25 Gordon Street. [see grid  D1 on the  UCL map]