{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Qiu C"],"funding":["National Institute of Environmental Health Sciences","Department of Energy","NINDS NIH HHS","National Institutes of Health"],"pagination":["536-548"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8754657"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["50(1)"],"pubmed_abstract":["In C. elegans, PUF proteins promote germline stem cell self-renewal. Their functions hinge on partnerships with two proteins that are redundantly required for stem cell maintenance. Here we focus on understanding how the essential partner protein, LST-1, modulates mRNA regulation by the PUF protein, FBF-2. LST-1 contains two nonidentical sites of interaction with FBF-2, LST-1 A and B. Our crystal structures of complexes of FBF-2, LST-1 A, and RNA visualize how FBF-2 associates with LST-1 A versus LST-1 B. One commonality is that FBF-2 contacts the conserved lysine and leucine side chains in the KxxL motifs in LST-1 A and B. A key difference is that FBF-2 forms unique contacts with regions N- and C-terminal to the KxxL motif. Consequently, LST-1 A does not modulate the RNA-binding affinity of FBF-2, whereas LST-1 B decreases RNA-binding affinity of FBF-2. The N-terminal region of LST-1 B, which binds near the 5' end of RNA elements, is essential to modulate FBF-2 RNA-binding affinity, while the C-terminal residues of LST-1 B contribute strong binding affinity to FBF-2. We conclude that LST-1 has the potential to impact which mRNAs are regulated depending on the precise nature of engagement through its functionally distinct FBF binding sites."],"journal":["Nucleic acids research"],"pubmed_title":["Bipartite interaction sites differentially modulate RNA-binding affinity of a protein complex essential for germline stem cell self-renewal."],"pmcid":["PMC8754657"],"funding_grant_id":["1ZIA50165","R01NS114018","R01 NS100788","R01NS100788","R01 NS114018"],"pubmed_authors":["Campbell ZT","Wine RN","Qiu C","Hall TMT"],"additional_accession":[]},"is_claimable":false,"name":"Bipartite interaction sites differentially modulate RNA-binding affinity of a protein complex essential for germline stem cell self-renewal.","description":"In C. elegans, PUF proteins promote germline stem cell self-renewal. Their functions hinge on partnerships with two proteins that are redundantly required for stem cell maintenance. Here we focus on understanding how the essential partner protein, LST-1, modulates mRNA regulation by the PUF protein, FBF-2. LST-1 contains two nonidentical sites of interaction with FBF-2, LST-1 A and B. Our crystal structures of complexes of FBF-2, LST-1 A, and RNA visualize how FBF-2 associates with LST-1 A versus LST-1 B. One commonality is that FBF-2 contacts the conserved lysine and leucine side chains in the KxxL motifs in LST-1 A and B. A key difference is that FBF-2 forms unique contacts with regions N- and C-terminal to the KxxL motif. Consequently, LST-1 A does not modulate the RNA-binding affinity of FBF-2, whereas LST-1 B decreases RNA-binding affinity of FBF-2. The N-terminal region of LST-1 B, which binds near the 5' end of RNA elements, is essential to modulate FBF-2 RNA-binding affinity, while the C-terminal residues of LST-1 B contribute strong binding affinity to FBF-2. We conclude that LST-1 has the potential to impact which mRNAs are regulated depending on the precise nature of engagement through its functionally distinct FBF binding sites.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2026-05-08T13:07:55.138Z","creation":"2022-02-11T16:19:02.123Z"},"accession":"S-EPMC8754657","cross_references":{"pubmed":["34908132"],"doi":["10.1093/nar/gkab1220"]}}