There are a limited number of mutually unreactive (orthogonal) chemical reactions ( 12) therefore, it is impractical to link more than a few building blocks in a one-pot reaction. Even the best noncovalent linkages ( 7– 9) or reversible covalent linkages, including disulfide bonds ( 10, 11), would allow rearrangement of polyproteams, so irreversible covalent linkage is required. Expressing modules individually and then linking the modules together would overcome these challenges as well as allow independent posttranslational modification of each module. Protein units can be joined genetically into one long open reading frame, but errors in protein synthesis and misfolding soon become limiting ( 5, 6). However, clustering different kinds of proteins into programmed polyprotein teams (“polyproteams”) is an unmet challenge ( 3, 4). Clustering a single kind of protein often greatly enhances biological signals ( 1), for example in the repeating antigen structures on vaccines ( 2). This simple and modular route to programmable “polyproteams” should enable exploration of a new area of biological space.īiological events usually depend on the cooperative activity of multiple proteins. Linear, branched, and combinatorial polyproteins were synthesized, identifying optimal combinations of ligands against death receptors and growth factor receptors for cancer cell death signal activation. Solid-phase attachment followed by sequential SpyTag or SnoopTag reaction between building-blocks enabled iterative extension. By engineering the adhesin RrgA from Streptococcus pneumoniae, we developed the peptide SnoopTag, which formed a spontaneous isopeptide bond to its protein partner SnoopCatcher with >99% yield and no cross-reaction to SpyTag/Sp圜atcher. SpyTag peptide is engineered to spontaneously form an isopeptide bond with Sp圜atcher protein. Here we achieved sequence-programmed irreversible connection of protein units, forming polyprotein teams by sequential amidation and transamidation. Reacting proteins together is more complex because of the number of reactive groups and delicate stability. Just as Buddhists sit in meditation and Hindus seek to unite their soul with Brahman, Rastas believe a divine essence sits at the core of every human being.Programmed connection of amino acids or nucleotides into chains introduced a revolution in control of biological function. Judging from his lengthy arrest record for marijuana possession, it seems Snoop Lion is already acquainted with a chief Rasta sacrament: smoking weed, or ganja, as many Jamaicans call it. Edmonds said some Rasta theology bears the influence of Hinduism, in which reincarnation is a core belief. Snoop Lion said he considers himself a reincarnation of the late musician. Rastafari holds that the late Ethiopian Emperor Haile Selassie was not only the messiah, he was descended from King Solomon and the Queen of Sheba.īob Marley, the reggae star and most famous Rasta, sang often of the "lion of Zion," referring to Selassie. Find the best pizza in Houston at these supreme pizzerias.Stroud? Most likely QB to fall to Houston Texans How a tiny Texas town set the stage for one the biggest Oscars battles ever.Houston Texans add familiar face at QB as free agency begins.Gigantic Valentine's Day asteroid could strike Earth in 2046, NASA says. ![]()
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