| First Author | Moritz L | Year | 2023 |
| Journal | Nat Struct Mol Biol | Volume | 30 |
| Issue | 8 | Pages | 1077-1091 |
| PubMed ID | 37460896 | Mgi Jnum | J:338968 |
| Mgi Id | MGI:7519103 | Doi | 10.1038/s41594-023-01033-4 |
| Citation | Moritz L, et al. (2023) Sperm chromatin structure and reproductive fitness are altered by substitution of a single amino acid in mouse protamine 1. Nat Struct Mol Biol |
| abstractText | Conventional dogma presumes that protamine-mediated DNA compaction in sperm is achieved by electrostatic interactions between DNA and the arginine-rich core of protamines. Phylogenetic analysis reveals several non-arginine residues conserved within, but not across species. The significance of these residues and their post-translational modifications are poorly understood. Here, we investigated the role of K49, a rodent-specific lysine residue in protamine 1 (P1) that is acetylated early in spermiogenesis and retained in sperm. In sperm, alanine substitution (P1(K49A)) decreases sperm motility and male fertility-defects that are not rescued by arginine substitution (P1(K49R)). In zygotes, P1(K49A) leads to premature male pronuclear decompaction, altered DNA replication, and embryonic arrest. In vitro, P1(K49A) decreases protamine-DNA binding and alters DNA compaction and 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 for reproductive fitness. |
