Crystallographic Analysis of Calcium-dependent Heparin Binding to Annexin A2
Annexin A2 and heparin bind to one another with high affinity and in a calcium-dependent manner, an interaction that may play a role in mediating fibrinolysis. In this study, three heparin-derived oligosaccharides of different lengths were co-crystallized with annexin A2 to elucidate the structural basis of the interaction. Crystal structures were obtained at high resolution for uncomplexed annexin A2 and three complexes of heparin oligosaccharides bound to annexin A2. The common heparin-binding site is situated at the convex face of domain IV of annexin A2. At this site, annexin A2 binds up to five sugar residues from the nonreducing end of the oligosaccharide. Unlike most heparin-binding consensus patterns, heparin binding at this site does not rely on arrays of basic residues; instead, main-chain and side-chain nitrogen atoms and two calcium ions play important roles in the binding. Especially significant is a novel calcium-binding site that forms upon heparin binding. Two sugar residues of the heparin derivatives provide oxygen ligands for this calcium ion. Comparison of all four structures shows that heparin binding does not elicit a significant conformational change in annexin A2. Finally, surface plasmon resonance measurements were made for binding interactions between annexin A2 and heparin polysaccharide in solution at pH 7.4 or 5.0. The combined data provide a clear basis for the calcium dependence of heparin binding to annexin A2.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 930213
- Report Number(s):
- BNL-80876-2008-JA; JBCHA3; TRN: US200822%%1392
- Journal Information:
- Journal of Biological Chemistry, Vol. 281; ISSN 0021-9258
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
AFFINITY
ATOMS
BASIC
CALCIUM
CALCIUM IONS
COMPLEXES
CONFORMATIONAL CHANGES
CRYSTAL STRUCTURE
DATA
FACE
FIBRINOLYSIS
HEPARIN
INTERACTIONS
LIGANDS
NITROGEN
OLIGOSACCHARIDES
OXYGEN
PLASMONS
POLYSACCHARIDES
RESIDUES
RESOLUTION
RESONANCE
SACCHAROSE
SOLUTIONS
SURFACES
national synchrotron light source