Thermodynamics of Charged Oligopeptide-Heparin Interactions

Mascotti, David P.; Lohman, Timothy M.

doi:10.1021/bi00009a022

Cited by 97 publications

(116 citation statements)

References 51 publications

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“…This is in agreement with recent studies showing that glycosaminoglycan-binding sites are typically extended clusters of positively charged amino acids distributed along the surface of a protein, or in a shallow groove [19] termed a 'cationic cradle' [20]. In addition, aromatic residues have been shown to contribute to the protein-heparin binding affinity [21]. It is therefore conceivable that tyrosine interacts with heparin by formation of hydrogen bonds between its hydroxyl group and the secondary alcoholic groups of the heparin carbohydrate units, and through a stacking interaction between the aromatic ring of tyrosine and the carbohydrate moieties of heparin.…”

Section: Discussionsupporting

confidence: 91%

Mapping the heparin‐binding domain of boar spermadhesins

et al. 1996

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Boar spermadhesins are a group of seminal plasma, heparin-binding proteins which appear to be involved in sperm capacitation and gamete interaction. Using a proteolytic protection assay we have identified regions of AQN-I, AQN-3, PSP-I and AWN which remain attached to a heparin-Sepharose column following in-column digestion of bound spermadhesins with chymotrypsin and elastase. In addition, the complete amino acid sequence of spermadhesin AWN was synthesized as overlapping peptides, and their ability to bind to a heparin-Sepharose column and to inhibit the interaction of soluble heparin with purified ELISA plate-coated AWN was tested. Both approaches gave similar results and as a whole showed that different regions of AWN may converge in its tertiary structure to form a composite heparin-binding site. The conformational heparin-binding surface resides on the GFCC'C" face of the proposed structural model for AWN and is in an opposite location to the carbohydratebinding region of the spermadhesin.

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Section: Discussionsupporting

confidence: 91%

Mapping the heparin‐binding domain of boar spermadhesins

et al. 1996

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“…Arginine binds tighter to heparin than lysine, since it has a higher potential for forming hydrogen bonds, and the guanidinium group may form an intrinsically stronger electrostatic interaction with a sulfate anion than the ammonium group (30). This has been clearly shown using non-collagenous heparin-binding peptides containing different proportions of arginine and lysine residues (30,31).…”

Section: Heparin-binding Capacity Of Colq Resides Exclusively In the mentioning

confidence: 96%

Two Different Heparin-binding Domains in the Triple-helical Domain of ColQ, the Collagen Tail Subunit of Synaptic Acetylcholinesterase

Deprez

Inestrosa

Krejci

2003

Journal of Biological Chemistry

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ColQ, the collagen tail subunit of asymmetric acetylcholinesterase, is responsible for anchoring the enzyme at the vertebrate synaptic basal lamina by interacting with heparan sulfate proteoglycans. To get insights about this function, the interaction of ColQ with heparin was analyzed. For this, heparin affinity chromatography of the complete oligomeric enzyme carrying different mutations in ColQ was performed. Results demonstrate that only the two predicted heparin-binding domains present in the collagen domain of ColQ are responsible for heparin interaction. Despite their similarity in basic charge distribution, each heparin-binding domain had different affinity for heparin. This difference is not solely determined by the number or nature of the basic residues conforming each site, but rather depends critically on local structural features of the triple helix, which can be influenced even by distant regions within ColQ. Thus, ColQ possesses two heparinbinding domains with different properties that may have non-redundant functions. We hypothesize that these binding sites coordinate acetylcholinesterase positioning within the organized architecture of the neuromuscular junction basal lamina.At vertebrate cholinergic synapses, acetylcholinesterase (AChE) 1 rapidly hydrolyzes the neurotransmitter acetylcholine, thereby terminating synaptic transmission. This key function does not only require a high catalytic turnover number but also a strategic positioning of the enzyme. This is achieved by the association of AChE catalytic subunits with structural subunits that bring them to the site of action. In the case of asymmetric AChE, the collagen ColQ is responsible for the localization of the enzyme at the vertebrate neuromuscular junction. Inactivation of the ColQ gene in mice or mutations in the human ColQ gene result in the absence of enzyme accumulation at the neuromuscular junction and are the cause of a congenital myasthenic syndrome (type 1c) (1, 2).As found in other collagens, ColQ contains a central triplehelical domain surrounded by non-collagenous N-and C-terminal domains (Fig. 1A). Each N-terminal domain organizes an AChE tetramer, so the triple-helical structure generates an A 12 or asymmetric AChE form with 12 catalytic subunits (3, 4). The collagen domain is characterized by Gly-Xaa-Yaa repeats and a high proportion of the stabilizing proline and hydroxyproline residues. The C-terminal domain is divided into a proline-rich region, important for triple-helix formation (5), and a cysteinerich region probably involved in the anchorage of AChE at the neuromuscular junction, since mutations in this region prevent the accumulation of AChE in congenital myasthenic syndrome type 1c patients (2).Heparan sulfate proteoglycans (HSPGs) have been implicated in the anchorage of asymmetric AChE to the synaptic basal lamina by interacting with ColQ through their heparan sulfate (HS) chains. This was proposed after showing that AChE could be specifically solubilized from the tissue with heparinase as well as with HS and ...

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“…When the lipoplexes interact with heparin and heparin sulphate, the negative charge of the polyelectrolytes determines NA release from the lipoplex through the same type of cooperative process that is responsible for lipoplex formation [136][137][138].…”

Section: Lipoplex Adhesion To the Cell Surfacementioning

confidence: 99%