{"doi":"10.1101/2021.09.16.460631","title":"Single residue substitution in protamine 1 disrupts sperm genome packaging and embryonic development in mice","abstract":"Summary Conventional dogma presumes that protamine-mediated DNA compaction in sperm is achieved by passive electrostatics between DNA and the arginine-rich core of protamines. However, phylogenetic analysis reveals several non-arginine residues that are conserved within, but not across, species. The functional significance of these residues or post-translational modifications are poorly understood. Here, we investigated the functional role of K49, a rodent-specific lysine residue in mouse protamine 1 (P1) that is acetylated early in spermiogenesis and retained in sperm. In vivo , an alanine substitution (P1 K49A) results in ectopic histone retention, decreased sperm motility, decreased male fertility, and in zygotes, premature P1 removal from paternal chromatin. In vitro , the P1 K49A substitution decreases protamine-DNA binding and alters DNA compaction/decompaction kinetics. Hence, a single amino acid substitution outside the P1 arginine core is sufficient to profoundly alter protein function and developmental outcomes, suggesting that protamine non-arginine residues are essential to ensure reproductive fitness.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":213892,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":741144,"name":"Samantha B. Schon","orcid":"0000-0001-5524-3649","position":1,"is_corresponding":false},{"id":807303,"name":"Mashiat Rabbani","orcid":null,"position":2,"is_corresponding":false},{"id":458335,"name":"Sheng Yi","orcid":"0000-0003-1316-3370","position":3,"is_corresponding":false},{"id":318819,"name":"Devon F. Pendlebury","orcid":null,"position":4,"is_corresponding":false},{"id":806508,"name":"Ritvija Agrawal","orcid":"0000-0002-7540-0987","position":5,"is_corresponding":false},{"id":203375,"name":"Caleb Sultan","orcid":null,"position":6,"is_corresponding":false},{"id":806509,"name":"Kelsey Jorgensen","orcid":"0000-0002-8681-5248","position":7,"is_corresponding":false},{"id":235828,"name":"Xianing Zheng","orcid":"0000-0002-3302-1241","position":8,"is_corresponding":false},{"id":539752,"name":"Adam Diehl","orcid":"0000-0002-0915-4570","position":9,"is_corresponding":false},{"id":557057,"name":"Kaushik Ragunathan","orcid":"0000-0003-4776-8589","position":10,"is_corresponding":false},{"id":87797,"name":"Yueh-Chiang Hu","orcid":"0000-0002-7992-0525","position":11,"is_corresponding":false},{"id":277673,"name":"Jayakrishnan Nandakumar","orcid":"0000-0001-9146-2785","position":12,"is_corresponding":false},{"id":235834,"name":"Jun Z. Li","orcid":"0000-0001-6727-0812","position":13,"is_corresponding":false},{"id":242216,"name":"Alan P. Boyle","orcid":"0000-0002-2081-1105","position":14,"is_corresponding":false},{"id":235833,"name":"Kyle E. Orwig","orcid":"0000-0002-7952-8419","position":15,"is_corresponding":false},{"id":555960,"name":"Sy Redding","orcid":"0000-0003-3463-7985","position":16,"is_corresponding":false},{"id":235835,"name":"Saher Sue Hammoud","orcid":"0000-0002-5040-6370","position":17,"is_corresponding":false},{"id":658347,"name":"Lindsay Moritz","orcid":"0000-0001-6704-8453","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T23:52:41.672172Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}