Proteases universally recognize beta strands in their active sites

One way to combat infectious diseases is to selectively inhibit foreign proteases within host cells, thus retarding replication rates of infectious organisms and assisting normal immunological defense mechanisms involved in their eradication. This review gives a summary of over 1500 three dimensional crystal (X-ray) and solution (NMR) structures from the pdb of substrates, products and inhibitors bound in the active sites of aspartic, serine, metallo, cysteine, and threonine endopeptidases. These active sites of all five protease classes recognize peptidic and non-peptidic ligands in an extended beta strand conformation, with few exceptions. Comparisons of protease-bound ligand conformations are illustrated by structural superpositions for a subset of structures, including 21 aspartic, 44 serine, 20 metallo, 23 cysteine, and 2 threonine proteases, among the protease-ligand structures analyzed. The extended substrate-binding mode is also illustrated for 3 aspartic proteases, 1 serine protease, 1 cysteine protease and 1 metalloprotease

Guidelines for the use of flow cytometry and cell sorting in immunological studies

International audienceThe classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis