Plasminogen-binding group A streptococcal M-protein (PAM) is a signature surface virulence factor of specific strains of Group A Streptococcus pyogenes (GAS) and is an important tight binding protein for human plasminogen (hPg). After activation of PAM-bound hPg to the protease, plasmin (hPm), GAS cells develop invasive surfaces that are critical for their pathogenicity. PAMs are helical dimers in solution, which are sensitive to temperature changes over a physiological temperature range. We previously categorized PAMs into three classes (I–III) based on the number and nature of short tandem α-helical repeats (a1 and a2) in their NH2-terminal A-domains that dictate interactions with hPg/hPm. Class II PAMs are special cases since they only contain the a2-repeat, while Class I and Class III PAMs encompass complete a1a2-repeats. All dimeric PAMs tightly associate with hPg, regardless of their categories, but monomeric Class II PAMs bind to hPg much weaker than their Class I and Class III monomeric counterparts. Additionally, since the A-domains of Class II PAMs comprise different residues from other PAMs, the issue emerges as to whether Class II PAMs utilize different amino acid side chains for interactions with hPg. Herein, through NMR-refined structural analyses, we elucidate the atomic-level hPg-binding mechanisms adopted by two representative Class II PAMs. Furthermore, we develop an evolutionary model that explains from unique structural perspectives why PAMs develop variable A-domains with regard to hPg-binding affinity.
Skip Nav Destination
Article navigation
May 2020
-
Cover Image
Cover Image
Hot and cold spots in N-TIMP2 interacting with MMP-1 (green), MMP-3 (purple) and MMP-14 (blue). Each couple present 180° rotation with respect to each other. Hot spots (red) and cold spots (blue) are shown on the interface of N-TIMP2. To learn more about this, see the article by Aharon and colleagues (pp. 1701–1719) in this issue. The image was provided by Niv Papo.
Research Article|
May 05 2020
A local α-helix drives structural evolution of streptococcal M-protein affinity for host human plasminogen
Cunjia Qiu;
Cunjia Qiu
1W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
2Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
Search for other works by this author on:
Yue Yuan;
Yue Yuan
1W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
Search for other works by this author on:
Shaun W. Lee;
Shaun W. Lee
3Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
Search for other works by this author on:
Victoria A. Ploplis;
Victoria A. Ploplis
1W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
2Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
Search for other works by this author on:
Francis J. Castellino
1W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
2Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
Correspondence: Francis J. Castellino (fcastell@nd.edu)
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 06 2020
Revision Received:
April 07 2020
Accepted:
April 08 2020
Accepted Manuscript online:
April 09 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (9): 1613–1630.
Article history
Received:
March 06 2020
Revision Received:
April 07 2020
Accepted:
April 08 2020
Accepted Manuscript online:
April 09 2020
Citation
Cunjia Qiu, Yue Yuan, Shaun W. Lee, Victoria A. Ploplis, Francis J. Castellino; A local α-helix drives structural evolution of streptococcal M-protein affinity for host human plasminogen. Biochem J 15 May 2020; 477 (9): 1613–1630. doi: https://doi.org/10.1042/BCJ20200197
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.