<h3>Title</h3>
<h3><span style="font-size: 12.16px;">Protein degradation by a double-ring AAA+ protease: in singulo mechanisms of unfolding and translocation</span></h3>
<p><strong><span style="font-size: 12.16px;"><span style="text-decoration: underline;">Abstract</span> :</span></strong></p>
<p style="text-align: justify;"><span style="font-size: 12.16px;"> </span></p>
<p style="text-align: center;"><span style="font-size: 12.16px;"><img src="images/image-hemachandra.png" border="0" alt="" /></span></p>
<p style="text-align: justify;"><span style="font-size: 12.16px;">ATP powered molecular motors play a crucial role in maintaining protein quality control in a cell and AAA+ proteases maintain protein homeostasis by degrading damaged and unneeded proteins. Single-molecule manipulation tools complement the biochemical experiments and provide deeper insights into the mechanisms of these molecular motors and their interaction with protein substrates. In this talk, I will discuss my recent work on mechanistic investigations of a double-ring AAA+ protease, E.coli ClpAP using single-molecule optical tweezers and determine the role of individual ATPase rings in protein unfolding and translocation. Our single-molecule studies provide new insight into the functional importance of the D1 ring of ClpA and the role of coordination between the two AAA+ rings. Also, the differences in translocation from N- and -C termini indicate that the enzyme can recognize subtle differences in direction of the polypeptide track. In addition, I will elucidate the paramount role of local stability of a substrate in protein degradation and provide clues as to how the placement of degradation signals on a substrate may evolve to minimize the energetic cost of degradation.</span></p>
<p style="text-align: justify;"><span style="text-decoration: underline;">References</span>:</p>
<p style="text-align: justify;">Hema Chandra Kotamarthi, Robert Sauer, Tania Baker. “The non-dominant AAA+ ring in the ClpAP protease functions as an anti-stalling motor to accelerate protein unfolding and translocation” (Pre-peer reviewed version at bioarXiv: https://doi.org/10.1101/585554)</p>
<p style="text-align: justify;">Adrian Olivares*, Hema Chandra Kotamarthi*, Benjamin Stein, Robert Sauer, Tania Baker, “Effect of directional pulling on mechanical protein degradation by ATP-dependent proteolytic machines”, Proceedings of National Academy of Sciences, USA, 2017, Vol 114, E6306-E6313. * Equal Contribution.</p>