• UCSBgauchos twitter avatar
    .@UCSBMensSoccer puts up a fight vs. No. 2 Clemson, but falls 3-2 in Sweet 16. RECAP >>> https://t.co/oqnHQnJzTn https://t.co/vgP5NNdQpL
    13 hours 40 min ago
  • UCSBgauchos twitter avatar
    UCSB Falls at Arizona State on Last Second Shot, 70-68 https://t.co/J0qqsxzgGY
    14 hours 37 min ago
  • UCSBgauchos twitter avatar
    And that'll do it. They battled valiantly, but @UCSBMensSoccer's season comes to and w/ a 3-2 Sweet 16 loss at Clemson. Great season guys!
    15 hours 56 min ago
  • UCSBgauchos twitter avatar
    2 mins left here, rain is really pouring now. C'mon Gauchos!
    15 hours 58 min ago
  • UCSBgauchos twitter avatar
    Goal for Clemson. Tic-tac-toe passing leads to a tap-in goal for Kyle Murphy. 3-2 now w/ 11 mins to go #LetsGoGauchos
    16 hours 9 min ago
  • UCSBgauchos twitter avatar
    GOALLLLLLLL! Sloppy back pass from Clemson to the keeper, Kevin Feucht pounces on it and taps into an empty net. 2-2 w/ 20 mins left to go.
    16 hours 19 min ago
  • UCSBgauchos twitter avatar
    Clemson goes up 2-1 on a goal by Diego Campos. 22 mins left for UCSB to equalize.
    16 hours 23 min ago
  • UCSBgauchos twitter avatar
    63' - Yellow card for Clemson, #6 Paul Clowes
    16 hours 29 min ago
  • UCSBgauchos twitter avatar
    62' - Nice build up for UCSB leads to a shot from the right side from Ismail Jome, but he hits the sidenetting.
    16 hours 30 min ago
  • UCSBgauchos twitter avatar
    Tactical foul leading to the YC for Clemson leads to a short-side opportunity for Randy Mendoza, but his shot stays wide left.
    16 hours 37 min ago
  • UCSBgauchos twitter avatar
    58' - Yellow card for Clemson, #11 Aaron Jones
    16 hours 37 min ago
  • UCSBgauchos twitter avatar
    51' - Jome sends one to the far post from inside the 18, but his curler goes just wide.
    16 hours 44 min ago
  • UCSBgauchos twitter avatar
    Second half for @UCSBMensSoccer starting now, tied w/ No. 2 Clemson 1-1! Catch the end of the game here: https://t.co/R9FRG70Get
    16 hours 50 min ago
  • UCSBgauchos twitter avatar
    Halftime stats for UCSB/Clemson (tied 1-1) Shots: 8/5 Shots on Goal: 3/4 Corners: 3/2 Fouls: 13/8 Yellow cards: 1/0
    16 hours 59 min ago
  • UCSBgauchos twitter avatar
    Clemson equalizes late in the first half through an Aaron Jones strike. It's 1-1 heading into halftime.
    17 hours 6 min ago

Protein Knots Gain New Evolutionary Significance

Monday, June 4, 2012 - 17:00
Santa Barbara, CA


UCSB Mathematics professor Ken Millett

UCSB Mathematics professor Ken Millett


Full description below. †

A new study suggests that protein knots, a structure whose formation remains a mystery, may have specific functional advantages that depend on the nature of the protein's architecture.

"The presence of a knotted or slipknotted structure in a protein is relatively rare but really is very interesting," said Kenneth Millett, a professor of mathematics at UC Santa Barbara and a co-author of the paper, "Conservation of complex knotting and slipknotting patterns in proteins," published in the Proceedings of the National Academy of Sciences.

Relatively little is known about protein folding, the process by which a polypeptide chain with a specific sequence of amino acid chains forms the three-dimensional structures –– their "native states" –– required to become functional. How this process reproducibly achieves the required structure is the subject of intensive study. Even harder is understanding how this is accomplished for knotted proteins, where the chain loops around itself in entanglements of varying complexity; or the even rarer slipknotted proteins, where a loop is bound by another segment of the protein chain, similar to a shoelace bow.

What intrigued the scientists about the protein knots is that the folding process resulting in the formation of knots is intrinsically more difficult than the process producing unknotted proteins. The protein has to avoid not only energetic traps but also topological barriers. If an amino acid chain takes too much time to find its native state or if it is stuck in a misfolded or partially unfolded state, the result may be a useless protein or one that produces harm by causing protein aggregation which is known to cause neurodegenerative disorders.

"From an evolutionary point of view, knotting might seem unlikely to occur but, in fact, it does occur," said Millett, who, along with co-first authors Joanna Sulkowska from UC San Diego and Eric J. Rawdon from the University of Saint Thomas and with Jose N. Onuchic from Rice University and Andrzej Stasiak from the University of Lausanne, examined, analyzed, and classified 74,223 protein structures submitted to the Protein Data Bank for the location and formation of knots. Millett worked on the development of the mathematical theory and the computer implementation needed to identify the location and type of knots in the proteins studied in the paper.

What they found was that protein knots and slipknots, instead of being discarded through the process of evolution, are often strongly conserved. This suggests that, despite their reduced efficiency of folding, the knots are somehow advantageous and important to the function of the protein.

Additionally, the researchers found that the location of these knots and slipknots is highly conserved, marked by points of flexibility –– "hinges" –– in the chain that may have properties necessary for more efficient folding.

Knots and slipknots could contribute to the stability of the protein, as shown by the similar slipknot loops observed in several families of proteins that form transmembrane channels –– the ducts through membranes of a cell, that allow certain materials to pass through. The slipknot, according to the authors, seems to strap together several transmembrane structures giving stability and forming the channel needed to allow passage through cell membranes.

The researchers will continue their study of the little-understood process of protein folding and knotting, said Millett.

"These knots may help to identify features that turn out to be important, and aspects of the structure that are more generalizable. We need to clearly understand how these things come to be, what are the implications of their structure, and how might one be able to somehow guide them," said Millett.








Bottom image: Molecular structures and matrix presentation for ubiquitin C-terminal hydrolases from (A) human, (B) yeast, and (C) P. falciparum plasmodium cells form the same knotting motif.



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