MOLECULAR MODELING OF PROTEIN-GLYCOSAMINOGLYCAN INTERACTIONS
MOLECULAR MODELING OF PROTEIN-GLYCOSAMINOGLYCAN INTERACTIONS
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DOI：
10.1161/01.atv.9.1.21
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发表时间：
1989-01-01
期刊：
影响因子：
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通讯作者：
WEINTRAUB, HJR
中科院分区：
文献类型：
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作者：
CARDIN, AD;WEINTRAUB, HJR
根据21种蛋白质的碱性和非碱性残基的序列组织，确定了49个区域为潜在的肝素结合位点。玻连蛋白、载脂蛋白E和B-100以及血小板因子4中的12个已知肝素结合序列被用于制定两个搜索字符串，用于识别其他蛋白中的潜在肝素结合区域。糖胺聚糖识别的共有序列确定为[-X-B-B-X-B-X]和[-X-B-B-B-X-X-B-X-]，其中B是碱性残基的概率，X是亲水性残基。预测，然后作出内皮细胞生长因子，红紫素，抗凝血酶-III的肝素结合域。符合这些共有基序的许多天然序列显示出突出的两亲周期性，具有α-螺旋和β-通过预测算法和圆二色性研究确定的链构象。玻连蛋白的肝素结合结构域被建模，并形成一个亲水性口袋，包裹并折叠在肝素八糖上，产生互补结构。我们认为，这些共识序列元素形成潜在的成核位点的聚阴离子在蛋白质中的识别，并可能提供一个有用的指南，在确定肝素结合区在其他蛋白质。蛋白质-糖胺聚糖相互作用在动脉粥样硬化的可能相关性进行了讨论。
Forty-nine regions in 21 proteins were identified as potential heparin-binding sites based on the sequence organizations of their basic and nonbasic residues. Twelve known heparin-binding sequences in vitronectin, apolipoproteins E and B-100, and platelet factor 4 were used to formulate two search strings for identifying potential heparin-binding regions in other proteins. Consensus sequences for glycosaminoglycan recognition were determined as [-X-B-B-X-B-X] and [-X-B-B-B-X-X-B-X-] where B is the probability of a basic residue and X is a hydropathic residue. Predictions were then made as to the heparin-binding domains in endothelial cell growth factor, purpurin, and antithrombin-III. Many of the natural sequences conforming to these consensus motifs show prominent amphipathic periodicities having both .alpha.-helical and .beta.-strand conformations as determined by predictive algorithms and circular dichroism studies. The heparin-binding domain of vitronectin was modeled and formed a hydrophilic pocket that wrapped around and folded over a heparin octasaccharide, yielding a complementary structure. We suggest that these consensus sequence elements form potential nucleation sites for the recognition of polyanions in proteins and may provide a useful guide in identifying heparin-binding regions in other proteins. The possible relevance of protein-glycosaminoglycans interactions in atherosclerosis is discussed.