KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Molecular Biosciences
    • Molecular Biosciences Scholarly Works
    • View Item
    •   KU ScholarWorks
    • Molecular Biosciences
    • Molecular Biosciences Scholarly Works
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    A de novo protein binding pair by computational design and directed evolution

    Thumbnail
    View/Open
    Karanicolas_2011.pdf (2.011Mb)
    Issue Date
    2011-04-22
    Author
    Karanicolas, John
    Corn, Jacob E.
    Chen, Irwin
    Joachimiak, Lukasz A.
    Dym, Orly
    Peck, Sun H.
    Albeck, Shira
    Unger, Tamar
    Hu, Wenxin
    Liu, Gaohua
    Delbecq, Scott
    Montelione, Gaetano
    Spiegel, Clint
    Liu, David R.
    Baker, David
    Publisher
    Elsevier
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Metadata
    Show full item record
    Abstract
    The de novo design of protein-protein interfaces is a stringent test of our understanding of the principles underlying protein-protein interactions and would enable new approaches to biological and medical challenges. Here we describe a novel motif-based method to computationally design protein-protein complexes with native-like interface composition and interaction density. Using this method we designed a pair of proteins, Prb and Pdar, that heterodimerize with a Kd of 130 nM, 1,000-fold tighter than any previously designed de novo protein-protein complex. Directed evolution identified two point mutations that improve affinity to 180 pM. Crystal structures of complexes containing designed and evolved proteins reveal binding is entirely through the designed interface, making use of specific designed interactions. Surprisingly, in the evolved complex one of the partners is rotated 180 degrees relative to the design model. This work demonstrates that current understanding of protein-protein interfaces is sufficient to rationally design interfaces de novo, and underscores remaining challenges.
    URI
    http://hdl.handle.net/1808/24585
    DOI
    https://doi.org/10.1016/j.molcel.2011.03.010
    Collections
    • Molecular Biosciences Scholarly Works [581]
    Citation
    Karanicolas, J., Corn, J. E., Chen, I., Joachimiak, L. A., Dym, O., Peck, S. H., … Baker, D. (2011). A de novo protein binding pair by computational design and directed evolution. Molecular Cell, 42(2), 250–260. http://doi.org/10.1016/j.molcel.2011.03.010

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps