A disease associated mutant reveals how Ltv1 orchestrates RP assembly and rRNA folding of the small ribosomal subunit head.

"thus the composite structure is consistent with and explains available data suggesting that it is correct at least in broad strokes although likely not in atomic detail 10 1371/journal pgen 1010862 g003 fig 3 (a) a structure for ltv1 was obtained from the alphafold website ( https://alphafold ebi ac uk/ ) and placed on the structure for pre-40s ribosomes (pdb id 6fai) by overlay with the enp1-binding alpha-helix.; because the resolution of the available cryo-em structures in that area is limited and does not unambiguously identify these three proteins and because the alphafold-predicted structure shows a different path for yeast ltv1 we first used genetic interactions to obtain evidence for interactions between ltv1 rps15 and tsr1 10 1371/journal pgen 1010862 g007 fig 7 (a) structure of the pre-40s ribosome highlighting residues altered in ribosomes from ltv1_l216s yeast as determined by dms-mapseq ( fig 6a and 6b ) showing tsr1 and ltv1 (from pdb id 6fai) (b) structure of the pre-40s ribosome with ltv1 and tsr1 in the position from earlier pre-40s (6fai purple) and from 80s-like ribosomes (in blue) near the beak (6wdr) 6fai and 6wdr were overlaid by matching the 18s rrna (c) structural detail of the complex in b viewed from the top of the subunit demonstrating that tsr1_early but not tsr1_late blocks binding and dissociation of ltv1 (d) summary of the genetic interaction network shown by the data in panel e and f and in s5 fig (e) doubling times (normalized to wt ltv1) for yeast cells expressing either wt ltv1 or ltv1_l216s in full length or truncated (at amino acid 394) form (f) doubling times (normalized to wt rps15) for yeast cells expressing either wt rps15 rps15_yrr (y123ir127kr130k) or rps15_rk (r137ek142e) and wt ltv1 or ltv1_l216s (g) doubling times (normalized to wt tsr1) for yeast cells expressing either wt tsr1 or tsr1_rk or tsr1?; raw data were deposited to the pride database under accession number pxd046239. reviewer #3: no ---------------------------------------------------- data deposition if you have submitted a research article or front matter that has associated data that are not suitable for deposition in a subject-specific public repository (such as genbank or arrayexpress) one way to make that data available is to deposit it in the dryad digital repository .; journalid=pgenetics&manu=pgenetics-d-23-00751r1 more information about depositing data in dryad is available at http://www datadryad org/depositing . residues exposed in the nob1 but not the tsr1-bound structure (after ltv1 dissociation) are shown in red and residues protected in that transition are shown in green space-fill (eps) click here for additional data file s1 table (docx) click here for additional data file s2 table (docx) click here for additional data file s3 table (docx) click here for additional data file s1 data (xlsx) click here for additional data file. file s3 table (docx) click here for additional data file s1 data (xlsx"

"The authors have declared that no competing interests exist.’"

"This work was supported by National Institute of Health grants R35-GM136323 and HHMI Faculty Scholar Grant 55108536 (to K.K.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."