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Kringle 2 mediates high affinity binding of plasminogen to an internal sequence in streptococcal surface protein PAM.

Wistedt, AC; Kotarsky, Heike LU ; Marti, D; Ringdahl, Ulrika LU ; Castellino, FJ; Schaller, J and Sjöbring, Ulf LU (1998) In The Journal of biological chemistry 273(38). p.24420-24424
Abstract
Many cells express receptors for plasminogen (Pg), although the responsible molecules in most cases are poorly defined. In contrast, the group A streptococcal surface protein PAM contains a domain with two 13-amino acid residue long repeated sequences (a1 and a2) responsible for Pg binding. Here we identify the region in Pg that interacts with PAM. A radiolabeled proteolytic plasminogen fragment containing the first three kringles (K1-K3) interacted with streptococci expressing PAM or a chimeric surface protein harboring the a1a2 sequence. In contrast, plasminogen fragments containing kringle 4 or kringle 5 and the activable serine proteinase domain failed to bind to PAM-expressing group A streptococci. A synthetic and a recombinant... (More)
Many cells express receptors for plasminogen (Pg), although the responsible molecules in most cases are poorly defined. In contrast, the group A streptococcal surface protein PAM contains a domain with two 13-amino acid residue long repeated sequences (a1 and a2) responsible for Pg binding. Here we identify the region in Pg that interacts with PAM. A radiolabeled proteolytic plasminogen fragment containing the first three kringles (K1-K3) interacted with streptococci expressing PAM or a chimeric surface protein harboring the a1a2 sequence. In contrast, plasminogen fragments containing kringle 4 or kringle 5 and the activable serine proteinase domain failed to bind to PAM-expressing group A streptococci. A synthetic and a recombinant polypeptide containing the a1a2 sequence both bound to immobilized recombinant K2 (rK2) but not to rK1 or rK3. The interaction between the a repeat region and rK2 was reversible, and rK2 completely blocked the binding of Pg to the a1a2 region. The binding of the a repeat containing polypeptide to K2 occurred with an equilibrium association constant of 4.5 x 10(7) M-1, as determined by surface plasmon resonance, a value close to that (1.6 x 10(7) M-1) calculated for the a1a2-Pg interaction. Inhibition experiments suggested involvement of the lysine-binding site of K2 in the interaction. These data demonstrate that K2 contains the major Pg-binding site for PAM, providing the first well defined example of an interaction between an internal Pg-binding region in a protein and a single kringle domain. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
The Journal of biological chemistry
volume
273
issue
38
pages
24420 - 24424
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • Scopus:0032544354
language
English
LU publication?
yes
id
ea45e4e8-58db-4115-a820-89a63092cc01 (old id 1216545)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/9733732
http://www.jbc.org/content/273/38/24420.long
date added to LUP
2013-10-09 15:46:23
date last changed
2016-04-16 11:05:10
@misc{ea45e4e8-58db-4115-a820-89a63092cc01,
  abstract     = {Many cells express receptors for plasminogen (Pg), although the responsible molecules in most cases are poorly defined. In contrast, the group A streptococcal surface protein PAM contains a domain with two 13-amino acid residue long repeated sequences (a1 and a2) responsible for Pg binding. Here we identify the region in Pg that interacts with PAM. A radiolabeled proteolytic plasminogen fragment containing the first three kringles (K1-K3) interacted with streptococci expressing PAM or a chimeric surface protein harboring the a1a2 sequence. In contrast, plasminogen fragments containing kringle 4 or kringle 5 and the activable serine proteinase domain failed to bind to PAM-expressing group A streptococci. A synthetic and a recombinant polypeptide containing the a1a2 sequence both bound to immobilized recombinant K2 (rK2) but not to rK1 or rK3. The interaction between the a repeat region and rK2 was reversible, and rK2 completely blocked the binding of Pg to the a1a2 region. The binding of the a repeat containing polypeptide to K2 occurred with an equilibrium association constant of 4.5 x 10(7) M-1, as determined by surface plasmon resonance, a value close to that (1.6 x 10(7) M-1) calculated for the a1a2-Pg interaction. Inhibition experiments suggested involvement of the lysine-binding site of K2 in the interaction. These data demonstrate that K2 contains the major Pg-binding site for PAM, providing the first well defined example of an interaction between an internal Pg-binding region in a protein and a single kringle domain.},
  author       = {Wistedt, AC and Kotarsky, Heike and Marti, D and Ringdahl, Ulrika and Castellino, FJ and Schaller, J and Sjöbring, Ulf},
  language     = {eng},
  number       = {38},
  pages        = {24420--24424},
  publisher    = {ARRAY(0xa8274d0)},
  series       = {The Journal of biological chemistry},
  title        = {Kringle 2 mediates high affinity binding of plasminogen to an internal sequence in streptococcal surface protein PAM.},
  volume       = {273},
  year         = {1998},
}