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Comparative analysis of structurally defined heparin binding sequences reveals a distinct spatial distribution of
H Margalit1, N Fischer, S A Ben-Sasson
1Department of Molecular Genetics, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
The Journal of Biological Chemistry
|September 15, 1993
Summary
Researchers identified a common structural motif in heparin-binding proteins. This motif, featuring specific basic amino acid arrangements, explains how heparin interacts with proteins at a molecular level, clarifying its physiological roles.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Heparin, a well-studied glycosaminoglycan, plays crucial roles in numerous physiological processes.
- Many proteins bind to heparin, modulating their activities, but the molecular mechanisms remain unclear due to a lack of structural data on heparin-protein complexes.
Purpose of the Study:
- To explore the molecular mechanism of heparin-protein interactions by identifying common structural motifs in heparin-binding sequences.
- To elucidate the structural basis for heparin's modulation of protein activity.
Main Methods:
- Compiled a database of experimentally validated heparin-binding protein sequences.
- Analyzed the spatial distribution of basic amino acid residues in peptides with known three-dimensional structures.
- Utilized computer graphics to identify common structural patterns.
Main Results:
- Identified a unique spatial distribution of basic amino acids in heparin-binding segments, often featuring two basic residues (commonly arginine) approximately 20 Å apart on an alpha-helix.
- Observed an amphipathic structure with basic residues on one side and nonpolar residues on the opposite side.
- Found that similar arrangements in beta-strands are also compatible with heparin binding, suggesting a 20-Å interval accommodates a pentasaccharide, leading to an intertwined complex.
Conclusions:
- The identified common motif provides a structural basis for heparin-protein interactions at the molecular level.
- The proposed intertwinement model explains how heparin binding influences protein activity.
- Further investigation into the dynamics of this interaction could reveal mechanisms underlying changes in protein function.