Structural Study Of Ribosomes From Human Pathogens

The ribosome is responsible for protein biosynthesis in all living organisms,and also plays diverse roles in regulating various cellular activities.Prokaryotic ribosome is consisted of 3 r RNA and 54 proteins.Ribosomes isolated from prokaryotes are well-conserved.Eukaryotic ribosome is composed of 4 r RNA and about 80 proteins.However,ribosomal proteins and r RNAs from different eukaryotes show significant diversity.Meanwhile,ribosome is a key target for many antibiotics or small-molecule inhibitors.High-resolution ribosomes structures are of importance for structure-based drug design.In this study,we solve the eukaryotic ribosomes structures at near atomic resolution from human parasites Trichomonas vaginalis and Toxoplasma gondii and prokaryotic ribosome structure from Mycobacterium smegmatis,which is the model of Mycobacterium tubercolusis.We have determined the structure of cytosolic ribosome from T.vaginalis at the overall resolution of 3.3 ?.Though ribosome of T.vaginalis owns the same amount of 4 r RNA and 79 ribosomal proteins as some other eukaryotic ribosomes,the r RNA expansion segements ES3 S,ES6S,ES9 L,ES39L are largely shortened and ES7 L,ES27L,ES31 L are totally missing.The r RNA of T.vaginalis are comparable to prokaryotic counterparts in size except the 5.8S which is not present in the prokaryotic ribosomes.Some eukaryote-specific bridges which are maintained by the eukaryote-specific counterparts are affected in the T.vaginalis ribosome.The overall resolution of cytosolic ribosome structure from T.gondii are 3.22 ?.Ribosome from T.gondii are similar to those from S.cerevisiae and P.falciparum.But,r RNA expansion segment ES7 L is lengthened in T.gondii compared to counterparts in S.cerevisiae and P.falciparum.The N terminus of ribosomal protein e L41 in T.gondii ribosome is longer,thus can interact with the r RNA helix h2.Compared with other high-resolution ribosomes structures,we find the co-evolution of r RNA expansion segments ES7 L,ES15L and ribosomal proteins e L6,e L28.The small and large subunits of Mycobacterium smegmatis are solved to the resolution of 3.45 ? and 3.08 ?,respectively.The most striking r RNA variable region is the H54 a in the large subunit.And this r RNA helix can contact the protein b S6 in the small subunit,forming another bridge which is not present in other known prokaryotic ribosomes.Besides,many other r RNA variable regions,H15,H16 a and H31 a are significantly different from other prokaryotic ribosomes.Ribosomal protein b L37,colse to the Peptidyl transferase center,is not present in other ribosomes.And Ribosomal protein u L41,considered to be existed in eukaryotic ribosomes is also present in the ribosomes from prokaryote Mycobacterium smegmatis.These two proteins which are close to the function center of ribosome,may be new target of anti-bubercolusis drugs.