Unraveling the Amino Acid Sequence Crucial for Heparin Binding to Collagen V

Delacoux, Frédéric; Fichard, Agnès; Cogne, Sylvain; Garrone, R.; Ruggiero, Florence

doi:10.1074/jbc.m004724200

Cited by 29 publications

(32 citation statements)

References 30 publications

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“…This may in part result from the indistinct requirements for "consensus" heparin binding motifs of proteins. Clusters of six to eight alternating basic amino acid residues have been shown to be the requisite factors for recognition of sulfated polysaccharides (2,20).…”

Section: Discussionmentioning

confidence: 99%

Insight into a Conserved Lifestyle: Protein-Carbohydrate Adhesion Strategies of Vector-Borne Pathogens

Dinglasan

Jacobs-Lorena

2005

Infect Immun

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The incidence of vector-borne diseases such as malaria, dengue, African sleeping sickness, and tick-borne fevers is increasing. Given that current global control efforts have met with limited success, the need to develop novel interventions has become all the more vital. Successful discovery of such interventions is contingent on improving our understanding of how the pathogen interacts with its vertebrate host and also with its invertebrate vector. In this review we examine a premise developed more than 20 years ago (94) that emphasized the role of protein-carbohydrate interactions in microbial pathogenesis, and we present it in the context of vector-pathogen dynamics.Glycans are "essential macromolecules for numerous cellular processes, such as signaling, structural-support, cell-cell interaction, cell-matrix adhesion, growth, protection and trafficking" (94). Their ubiquitous yet tissue-specific occurrence as cell surface glycoconjugates has, over evolutionary time, been exploited by several pathogenic microorganisms as receptors for attachment and invasion (95). While evidence for microbial adherence to mammalian glycolipids and glycoproteins continues to grow (for reviews see references 17, 18, 58, 95, and 115), only recently has evidence for a "protein-carbohydrate recognition strategy" for vector host-pathogen interactions emerged. This review focuses on the most recent advances that describe adherence mechanisms of three different classes of pathogens-bacteria, viruses, and protozoan parasites-to their obligate arthropod vectors. We also discuss how the proteincarbohydrate recognition strategies in both vector and mammalian life stages are apparently conserved and how this conservation could lead to the development of novel strategies for intervention.

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Section: Discussionmentioning

confidence: 99%

Insight into a Conserved Lifestyle: Protein-Carbohydrate Adhesion Strategies of Vector-Borne Pathogens

Dinglasan

Jacobs-Lorena

2005

Infect Immun

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“…KGHRG in ␣1(I) and KGIRGH in ␣2(I)) (28), whereas in collagens ␣1(V) 3 and ␣1(XI)␣2(XI)␣1(II) basic residues are spread throughout the sequence (i.e. KXGPRGXRGPTGPRGXR present in ␣1(V), ␣1(XI), and ␣2(XI) chains) (29). In ColQ, our results showed that the most important residues for heparin interaction are concentrated in the sequence GRPGBBGB, differing from those found in collagens.…”

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

confidence: 99%

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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“…Those experiments were carried out using the monomeric, non-triple-helical fragment HepV, and full-length, triple-helical isoforms of collagen V, namely the (␣1(V)) 2 ␣2 heterotrimer and the (␣1(V)) 3 homotrimer. The dependence of the interaction between collagen V and heparin/heparan sulfate upon the triple-helical conformation of collagen V was also investigated with a triple-helical synthetic peptide containing the 15 amino acid residues of the previously defined heparin binding site (10). Taken altogether, these results emphasize differences between the binding of the HepV fragment and of the full-length collagen V molecules to heparan sulfate.…”

mentioning

confidence: 70%

“…The recombinant production of HepV in Escherichia coli has set the stage for identifying the heparin binding site by site-directed mutagenesis and affinity chromatography. We have previously identified within the Lys 905 -Arg 921 sequence of the ␣1(V) chain five basic residues participating in the binding of HepV to heparin (10), but the molecular features of heparin responsible for the specific recognition of HepV have not been characterized, although the characteristics of heparin/heparan sulfate-protein interactions have been elucidated for several other proteins (for reviews, see Refs. 11 and 12).…”

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confidence: 99%

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Structural Requirements for Heparin/Heparan Sulfate Binding to Type V Collagen

Ricard‐Blum

Beraud

Raynal

et al. 2006

Journal of Biological Chemistry

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Collagen-proteoglycan interactions participate in the regand native collagen V molecules formed much more stable complexes with heparin than HepV, and collagen V bound to heparin/heparan sulfate with a higher affinity (in the nanomolar range) than HepV. Heat and chemical denaturation strongly decreased the binding, indicating that the triple helix plays a major role in stabilizing the interaction with heparin. Collagen V and HepV may play different roles in cell-matrix interactions and in matrix assembly or remodeling mediated by their specific interactions with heparan sulfate.Proteoglycans are widely distributed at the cell surface and in the extracellular matrix. They consist of a protein core to which one or more glycosaminoglycan side chains are covalently attached, conferring a strong negative charge on proteoglycans (1, 2). Interactions of proteoglycans with a number of matrix proteins, including collagens, are important in regulating cell behavior and fibril formation during development and pathophysiological events. Interactions with collagens can be dependent on the proteoglycan core protein or on the glycosaminoglycan chains. The heparan sulfate chain has various important biological properties and influences cell behavior through interactions with a variety of matrix proteins. Heparin binding sites have been identified and characterized in a wide range of matrix proteins, including collagens, but the structural requirements for heparan sulfate to bind these proteins are not fully understood.Collagen V, although a quantitatively minor component of connective tissues, plays a crucial role in matrix organization. Several isoforms of collagen V, including hybrid molecules containing collagen XI chains (3), occur in tissues, but the predominant molecular form is the heterotrimer (␣1(V)) 2 ␣2(V), whereas the ␣1(V)␣2(V)␣3(V) molecule and the (␣1(V)) 3 homotrimer are minor isoforms with a more restricted tissue distribution. Collagen V interacts with proteoglycans, which are widely distributed at the cell surface and in the extracellular matrix. It binds to the two small proteoglycans, decorin and biglycan, to the proteoglycan form of macrophage colony-stimulating factor (4), to the membrane chondroitin sulfate proteoglycan NG2 (5), and to syndecan-1 (6, 7). Binding to collagen V involves either the core protein or the glycosaminoglycan chains. Collagen V was shown to bind heparin through a 12-kDa fragment of the ␣1(V) chain referred to as HepV. Interestingly, we also showed that the recombinant HepV fragment supports heparin-dependent cell adhesion (8). The binding site for heparin is found in the ␣1 chain of collagen V, whereas the two other chains of collagen V, ␣2(V) and ␣3(V), do not bind to heparin. Sequence alignment of ␣ chains of collagens V and XI indicated that these two collagen types may use a common sequence motif to interact with heparin. This hypothesis was confirmed experimentally by others (9). The recombinant production of HepV in Escherichia coli has set the stage for identifying the hepa...

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Unraveling the Amino Acid Sequence Crucial for Heparin Binding to Collagen V

Cited by 29 publications

References 30 publications

Insight into a Conserved Lifestyle: Protein-Carbohydrate Adhesion Strategies of Vector-Borne Pathogens

Insight into a Conserved Lifestyle: Protein-Carbohydrate Adhesion Strategies of Vector-Borne Pathogens

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

Structural Requirements for Heparin/Heparan Sulfate Binding to Type V Collagen

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