The dystroglycan (DG) adhesion complex is formed by the peripheral alpha-DG and the transmembrane beta-DG, both originating from the same precursor. alpha-DG plays a crucial role for tissue stability since it binds with high affinity a variety of proteins and proteoglycans in many different cell types. One common molecular feature of most of the alpha-DG ligands is the presence of laminin globular (LG) domains that are likely to interact with some of the carbohydrates protruding from the mucin-like region of alpha-DG. Every tissue is supposed to produce a specific alpha-DG harboring a particular sugar moiety that will enable it to bind a specific ligand, but often several alpha-DG ligands are co-expressed within the same tissue. It is therefore very important to assess all these different interactions, ultimately measuring the affinity constants (K-Ds) underlying them. Herein, we present an updated list of alpha-DG interactors, including non LG-domains containing ligands, offering both a historic perspective on the original contributions made by several laboratories and an update on the different techniques used and the K-D values obtained so far. For the cure of some muscular dystrophies, the reinstatement of a prominent affinity between alpha-DG and one of its vicarious ligands is becoming an increasingly popular choice for strengthening the basement membrane-tissue connection. An update on the current available information about alpha-DG's multiple, and often "concomitant" affinities, may be of interest for those wishing to better direct their molecular therapy approaches. A final paragraph is dedicated to comment on the evidence that an increase in affinity is not always advantageous.
The Multiple Affinities of alpha-Dystroglycan
Sciandra Francesca;Bozzi Manuela;Brancaccio Andrea
2013
Abstract
The dystroglycan (DG) adhesion complex is formed by the peripheral alpha-DG and the transmembrane beta-DG, both originating from the same precursor. alpha-DG plays a crucial role for tissue stability since it binds with high affinity a variety of proteins and proteoglycans in many different cell types. One common molecular feature of most of the alpha-DG ligands is the presence of laminin globular (LG) domains that are likely to interact with some of the carbohydrates protruding from the mucin-like region of alpha-DG. Every tissue is supposed to produce a specific alpha-DG harboring a particular sugar moiety that will enable it to bind a specific ligand, but often several alpha-DG ligands are co-expressed within the same tissue. It is therefore very important to assess all these different interactions, ultimately measuring the affinity constants (K-Ds) underlying them. Herein, we present an updated list of alpha-DG interactors, including non LG-domains containing ligands, offering both a historic perspective on the original contributions made by several laboratories and an update on the different techniques used and the K-D values obtained so far. For the cure of some muscular dystrophies, the reinstatement of a prominent affinity between alpha-DG and one of its vicarious ligands is becoming an increasingly popular choice for strengthening the basement membrane-tissue connection. An update on the current available information about alpha-DG's multiple, and often "concomitant" affinities, may be of interest for those wishing to better direct their molecular therapy approaches. A final paragraph is dedicated to comment on the evidence that an increase in affinity is not always advantageous.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
