Kringle 2 mediates high affinity binding of plasminogen to an internal sequence in streptococcal surface protein PAM.
(1998) In 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1216545
- author
- Wistedt, AC ; Kotarsky, Heike LU ; Marti, D ; Ringdahl, Ulrika LU ; Castellino, FJ ; Schaller, J and Sjöbring, Ulf LU
- organization
- publishing date
- 1998
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 273
- issue
- 38
- pages
- 24420 - 24424
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- scopus:0032544354
- ISSN
- 1083-351X
- 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
- 2016-04-04 13:21:06
- date last changed
- 2022-01-30 00:08:17
@article{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}},
issn = {{1083-351X}},
language = {{eng}},
number = {{38}},
pages = {{24420--24424}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Kringle 2 mediates high affinity binding of plasminogen to an internal sequence in streptococcal surface protein PAM.}},
url = {{http://www.ncbi.nlm.nih.gov/pubmed/9733732}},
volume = {{273}},
year = {{1998}},
}