Galectin-1 (Gal-1) is a galactose-binding protein involved in various cellular functions. Gal-1's activity has been suggested to be connected to two molecular concepts, which are, however, lacking experimental proof: a) enhanced binding affinity of Gal-1 toward membranes containing monosialotetrahexosylganglioside (GM1) over disialoganglioside GD1a and b) cross-linking of GM1's by homodimers of Gal-1. We provide evidence about the specificity and the nature of the interaction of Gal-1 with model membranes containing GM1 or GD1a, employing a broad panel of fluorescence-based and label-free experimental techniques, complemented by atomistic biomolecular simulations. Our study demonstrates that Gal-1 indeed binds specifically to GM1 and not to GD1a when embedded in membranes over a wide range of concentrations (i.e., 30 nM to 20 μM). The apparent binding constant is about tens of micromoles. On the other hand, no evidence of Gal-1/GM1 cross-linking was observed. Our findings suggest that cross-linking does not result from sole interactions between GM1 and Gal-1, indicating that in a physiological context, additional triggers are needed, which shift the GM1/Gal-1 equilibria toward the membrane-bound homodimeric Gal-1.

Consiglio Nazionale delle Ricerche Istituto di Cristallografia Via P Gaifami 18 Catania 95126 Italy

Department of Physics University of Helsinki P O Box 64 Helsinki FI 00014 Finland

Department of Veterinary Science Chair of Biochemistry and Chemistry Ludwig Maximilians University Munich Lena Christ Str 48 Planegg 82152 Germany

Dipartimento di Scienze Chimiche Università degli Studi di Catania Viale A Doria 6 Catania 95125 Italy

J Heyrovský Institute of Physical Chemistry of the CAS v v i Dolejškova 2155 3 Prague 8 182 23 Czech Republic

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