scholarly journals Interactions of integrin GPIIb/IIIa-derived peptides with fibrinogen investigated by NMR spectroscopy

1996 ◽  
Vol 315 (1) ◽  
pp. 161-170 ◽  
Author(s):  
Letitia J. YAO ◽  
Kevin H. MAYO
Keyword(s):  
Nmr Spectroscopy ◽  
Bound States ◽  
Distance Geometry ◽  
Integrin Receptor ◽  
Hydrophobic Residues ◽  
Fibrinogen Binding ◽  
Nuclear Overhauser ◽  
Nuclear Overhauser Effects ◽  
Exchange Regime ◽  
Positively Charged

Three peptides derived from platelet integrin receptor glycoprotein αIIbβ3 (GPIIb/IIIa) have been identified recently as fibrinogen-binding sequences: GPIIb 300–314 and 656–667 and GPIIIa 211–223. NMR spectroscopy has been used here to investigate the interactions of these peptides with parent fibrinogen. Based on resonance broadening and chemical-shift changes of peptides in the presence and absence of fibrinogen, interactions in the fast ligand-exchange regime are apparent and interfacial residues can be proposed. Positively charged arginines and histidines, along with several hydrophobic residues, are implicated as being crucial to the binding process. Transferred nuclear Overhauser effects and distance geometry calculations allow discussion of probable conformations in peptide-‘bound’ states. These identifications are consistent with other biological/ chemical data and provide the basis for further studies aimed at understanding fibrinogen-mediated platelet aggregation on the molecular level.

scholarly journals NMR solution conformation of heparin-derived tetrasaccharide

1996 ◽  
Vol 318 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Dmitri MIKHAILOV ◽  
Kevin H. MAYO ◽  
Ioncho R. VLAHOV ◽  
Toshihiko TOIDA ◽  
Azra PERVIN ◽  
...  
Keyword(s):  
Chair Conformation ◽  
Coupling Constants ◽  
Solution Conformation ◽  
1H And 13C Nmr ◽  
Small Deviations ◽  
J Coupling Constants ◽  
Nuclear Overhauser ◽  
Nuclear Overhauser Effects ◽  
Dynamics Simulations ◽  
Ring Conformations

The solution conformation of the homogeneous, heparin-derived tetrasaccharide ΔUA2S(1 → 4)-α-d-GlcNpS6S(1 → 4)-α-l-IdoAp2S(1 → 4)-α-d-GlcNpS6S (residues A, B, C and D respectively, where IdoA is iduronic acid) has been investigated by using 1H- and 13C-NMR. Ring conformations have been defined by J-coupling constants and inter-proton nuclear Overhauser effects (NOEs), and the orientation of one ring with respect to the other has been defined by inter-ring NOEs. NOE-based conformational modelling has been done by using the iterative relaxation matrix approach (IRMA), restrained molecular dynamics simulations and energy minimization to refine structures and to distinguish between minor structural differences and equilibria between various ring forms. Both glucosamine residues B and D are in the 4C1 chair conformation. The 6-O-sulphate group is oriented in the gauche–trans configuration in the D ring, whereas in the B ring the gauche–gauche rotomer predominates. Uronate (A) and iduronate (C) residues are mostly represented by 1H2 and 2S0 twisted boat forms, respectively, with small deviations in expected coupling constants and NOEs suggesting minor contributions from other A and C ring conformations.

Investigation of the structure of regulatory proteins interacting with glycosaminoglycans by combining NMR spectroscopy and molecular modeling – the beginning of a wonderful friendship

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Georg Künze ◽  
Daniel Huster ◽  
Sergey A. Samsonov
Keyword(s):  
Nmr Spectroscopy ◽  
Structural Information ◽  
Md Simulations ◽  
Specific Protein ◽  
Regulatory Proteins ◽  
Structural Constraints ◽  
Modeling Tools ◽  
Nuclear Overhauser ◽  
Nmr Methods ◽  
High Flexibility

Abstract The interaction of regulatory proteins with extracellular matrix or cell surface-anchored glycosaminoglycans (GAGs) plays important roles in molecular recognition, wound healing, growth, inflammation and many other processes. In spite of their high biological relevance, protein-GAG complexes are significantly underrepresented in structural databases because standard tools for structure determination experience difficulties in studying these complexes. Co-crystallization with subsequent X-ray analysis is hampered by the high flexibility of GAGs. NMR spectroscopy experiences difficulties related to the periodic nature of the GAGs and the sparse proton network between protein and GAG with distances that typically exceed the detection limit of nuclear Overhauser enhancement spectroscopy. In contrast, computer modeling tools have advanced over the last years delivering specific protein-GAG docking approaches successfully complemented with molecular dynamics (MD)-based analysis. Especially the combination of NMR spectroscopy in solution providing sparse structural constraints with molecular docking and MD simulations represents a useful synergy of forces to describe the structure of protein-GAG complexes. Here we review recent methodological progress in this field and bring up examples where the combination of new NMR methods along with cutting-edge modeling has yielded detailed structural information on complexes of highly relevant cytokines with GAGs.

Sign in / Sign up

Export Citation Format

Share Document