History LSm

1 history

1.1 discovery of smith antigen
1.2 sm proteins, snrnps, spliceosome , messenger rna splicing
1.3 discovery of proteins similar sm proteins
1.4 discovery of lsm fold

history
discovery of smith antigen

the story of discovery of first lsm proteins begins young woman, stephanie smith, diagnosed in 1959 systemic lupus erythematosus (sle), succumbing complications of disease in 1969 @ age of 22. during period, treated @ new york s rockefeller university hospital, under care of dr. henry kunkel , dr. eng tan. autoimmune disease, sle patients produce antibodies antigens in cells nuclei, own dna. however, dr. kunkel , dr. tan found in 1966 ms. smith produced antibodies set of nuclear proteins, named smith antigen (sm ag). 30% of sle patients produce antibodies these proteins, opposed double stranded dna. discovery improved diagnostic testing sle, nature , function of antigen unknown.

sm proteins, snrnps, spliceosome , messenger rna splicing

research continued during 1970s , 1980s. smith antigen found complex of ribonucleic acid (rna) molecules , multiple proteins. set of uridine-rich small nuclear rna (snrna) molecules part of complex, , given names u1, u2, u4, u5 , u6. 4 of these snrnas (u1, u2, u4 , u5) found tightly bound several small proteins, named smb, smd, sme, smf, , smg in decreasing order of size. smb has alternatively spliced variant, smb , , similar protein, smn, replaces smb /b in (mostly neural) tissues. smd later discovered mixture of 3 proteins, named smd1, smd2 , smd3. these 9 proteins (smb, smb , smn, smd1, smd2, smd3, sme, smf , smg) became known sm core proteins, or sm proteins. snrnas complexed sm core proteins , other proteins form particles in cell s nucleus called small nuclear ribonucleoproteins, or snrnps. mid 1980s, became clear these snrnps form large (4.8 md molecular weight) complex, called spliceosome, around pre-mrna, excising portions of pre-mrna called introns , splicing coding portions (exons) together. after few more modifications, spliced pre-mrna becomes messenger rna (mrna) exported nucleus , translated protein ribosomes.

discovery of proteins similar sm proteins

the snrna u6 (unlike u1, u2, u4 , u5) not associate sm proteins, though u6 snrnp central component in spliceosome. in 1999 protein heteromer found binds u6, , consisted of 7 proteins homologous sm proteins. these proteins denoted lsm (like sm) proteins (lsm1, lsm2, lsm3, lsm4, lsm5, lsm6 , lsm7), similar lsm8 protein identified later. in bacterium escherichia coli, sm-like protein hf-i encoded gene hfq described in 1968 essential host factor rna bacteriophage qβ replication. genome of saccharomyces cerevisiae (baker s yeast) sequenced in mid-1990s, providing rich resource identifying homologs of these human proteins. subsequently, more eukaryotes genomes sequenced, became clear eukaryotes, in general, share homologs same set of 7 sm , 8 lsm proteins. after, proteins homologous these eukaryote lsm proteins found in archaea (sm1 , sm2) , bacteria (hfq , ylxs homologs). interestingly, archaeal lsm proteins more similar eukaryote lsm proteins either bacterial lsm proteins. lsm proteins described far rather small proteins, varying 76 amino acids (8.7 kd molecular weight) human smg 231 amino acids (29 kd molecular weight) human smb. recently, larger proteins have been discovered include lsm structural domain in addition other protein structural domains (such lsm10, lsm11, lsm12, lsm13, lsm14, lsm15, lsm16, ataxin-2, archaeal sm3).

discovery of lsm fold

around 1995, comparisons between various lsm homologs identified 2 sequence motifs, 32 nucleic acids long (14 amino acids), similar in each lsm homolog, , separated non-conserved region of variable length. indicated importance of these 2 sequence motifs (named sm1 , sm2), , suggested lsm protein genes evolved single ancestral gene. in 1999, crystals of recombinant sm proteins prepared, allowing x-ray crystallography , determination of atomic structure in 3 dimensions. demonstrated lsm proteins share similar three-dimensional fold of short alpha helix , five-stranded folded beta sheet, subsequently named lsm fold. other investigations found lsm proteins assemble torus (doughnut-shaped ring) of 6 or 7 lsm proteins, , rna binds inside of torus, 1 nucleotide bound each lsm protein.