6 research outputs found
Ariel - Volume 4 Number 2
Editors
David A. Jacoby
Eugenia Miller
Tom Williams
Associate Editors
Paul Bialas
Terry Burt
Michael Leo
Gail Tenikat
Editor Emeritus and Business Manager
Richard J. Bonnano
Movie Editor
Robert Breckenridge
Staff
Richard Blutstein
Mary F. Buechler
Steve Glinks
Len Grasman
Alice M. Johnson
J. D. Kanofsky
Tom Lehman
Dave Mayer
Bernie Odd
Design of a peptidic inhibitor that targets the dimer interface of a prototypic galectin
Localization of protein-binding sites within families of proteins
We address the question of whether or not the positions of protein-binding sites on homologous protein structures are conserved irrespective of the identities of their binding partners. First, for each domain family in the Structural Classification of Proteins (SCOP), protein-binding sites are extracted from our comprehensive database of structurally defined binary domain interactions (PIBASE). Second, the binding sites within each family are superposed using a structural alignment of its members. Finally, the degree of localization of binding sites within each family is quantified by comparing it with localization expected by chance. We found that 72% of the 1847 SCOP domain families in PIBASE have binding sites with localization values greater than expected by chance. Moreover, 554 (30%) of these families have localizations that are statistically significant (i.e., more than four standard deviations away from the mean expected by chance). In contrast, only 144 (8%) families have significantly low localization. The absence of a significant correlation of the binding site localization with the average sequence and structural conservations in a family suggests that localization can be helpful for describing the functional diversity of protein–protein interactions, complementing measures of sequence and structural conservation. Consideration of the binding site localization may also result in spatial restraints for the modeling of protein assembly structures
Re-wiring regulatory cell networks in immunity by galectin-glycan interactions
Programs that control immune cell homeostasis are orchestrated through the coordinated action of a number of regulatory cell populations, including regulatory T cells, regulatory B cells, myeloid-derived suppressor cells, alternatively-activated macrophages and tolerogenic dendritic cells. These regulatory cell populations can prevent harmful inflammation following completion of protective responses and thwart the development of autoimmune pathology. However, they also have a detrimental role in cancer by favoring escape from immune surveillance. One of the hallmarks of regulatory cells is their remarkable plasticity as they can be positively or negatively modulated by a plethora of cytokines, growth factors and co-stimulatory signals that tailor their differentiation, stability and survival. Here we focus on the emerging roles of galectins, a family of highly conserved glycan-binding proteins in regulating the fate and function of regulatory immune cell populations, both of lymphoid and myeloid origins. Given the broad distribution of circulating and tissue-specific galectins, understanding the relevance of lectin-glycan interactions in shaping regulatory cell compartments will contribute to the design of novel therapeutic strategies aimed at modulating their function in a broad range of immunological disorders.Fil: Blidner, Ada Gabriela. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental (i); ArgentinaFil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental (i); ArgentinaFil: Cagnoni, Alejandro. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental (i); ArgentinaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentin