Abstract:
:Recent studies indicate that binding of the urokinase-type plasminogen activator (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes, including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known about the exact mode of uPAR/uPA interactions or the presumed conformational changes that accompany uPA/uPAR engagement. Here, we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell-surface anchoring sequence, in complex with the amino-terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 A. We report the 1.9 A crystal structure of free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR/uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Barinka C,Parry G,Callahan J,Shaw DE,Kuo A,Bdeir K,Cines DB,Mazar A,Lubkowski Jdoi
10.1016/j.jmb.2006.08.063subject
Has Abstractpub_date
2006-10-20 00:00:00pages
482-95issue
2eissn
0022-2836issn
1089-8638pii
S0022-2836(06)01116-8journal_volume
363pub_type
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