Two different heparin-binding domains in the triple-helical domain of ColQ, the collagen tail subunit of synaptic acetylcholinesterase.
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 heparin-binding 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.
Deprez
Paola
P
Centro de Regulación Celular y Patología Dr Joaquín V Luco, Instituto Milenio de Biología Fundamental y Aplicada, Facultad de Ciencias Biológicas, P Universidad Católica de Chile. paola.deprez@bc.biol.ethz.ch
Inestrosa
Nibaldo C
NC
Krejci
Eric
E
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D024361:Amino Acids, Basic; D000818:Animals; D001665:Binding Sites; D002846:Chromatography, Affinity; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism; D006493:Heparin / Q000737:chemistry*; D009124:Muscle Proteins; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins
D024361:Amino Acids, Basic; D009124:Muscle Proteins; D011994:Recombinant Proteins; D006493:Heparin; D003094:Collagen; D000110:Acetylcholinesterase; C114027:COLQ protein, human