2I9A

Crystal structure of the free aminoterminal fragment of urokinase type plasminogen activator (ATF)

Summary for 2I9A

• Entry DOI: 10.2210/pdb2i9a/pdb
• Related: 2I9B
• Descriptor: Urokinase-type plasminogen activator, PHOSPHATE ION (3 entities in total)
• Functional Keywords: growth factor-like domain, kringle domain, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P00749
• Total number of polymer chains: 4
• Total formula weight: 65973.73

Authors

Lubkowski, J.,Barinka, C. (deposition date: 2006-09-05, release date: 2006-11-28, Last modification date: 2024-10-30)

Primary citation

Barinka, C.,Parry, G.,Callahan, J.,Shaw, D.E.,Kuo, A.,Bdeir, K.,Cines, D.B.,Mazar, A.,Lubkowski, J.
Structural basis of interaction between urokinase-type plasminogen activator and its receptor.
J.Mol.Biol., 363:482-495, 2006

PubMed 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.

PubMed: 16979660
DOI: 10.1016/j.jmb.2006.08.063

Experimental method

X-RAY DIFFRACTION (1.9 Å)