Exploring Structures and Dynamics of Protamine Molecules through Molecular Dynamics Simulations

Abstract

Protamines are arginine-rich proteins that condense DNA in sperm. Despite their importance in reproduction, information on protamine structure is scarce. We, therefore, used molecular dynamics to examine the structures of salmon, bull P1, and human P1 protamines. The sizes and shapes of each protamine varied widely, indicating that they were disordered with structures covering a broad conformational landscape, from hairpin loop structures to extended coils. Despite their general disorder, the protamines did form secondary structures, including helices and hairpin loops. In eutherians, hairpins may promote disulfide bonding that facilitates protamine-DNA condensation, but the specifics of this bonding is not well established. We examined inter-residue distances in the simulations to predict residue pairs likely to form intramolecular bonds, leading to the identification of bonding pairs consistent with previous results in bull and human. These results support a model for eutherian protamine structures where a highly charged center is surrounded by disulfide-bond-stabilized loops.

Reverse Engineering of a Pathogenic Antibody Reveals the Molecular Mechanism of Vaccine-Induced Immune Thrombotic Thrombocytopenia

“…The question of RVT1 cross-reactivity was approached in our work by using protamine as a model polycation. This choice was predicated on the fact that the polypeptides from the protamine family exhibit extremely high density of the positive charge (due to the incorporation of multiple poly-Arg segments in their sequences), while at the same time lacking any well-defined structure in solution . Analysis of the RVT1/protamine mixture with native MS provides clear evidence that a single antibody molecule readily accommodates up to two protamine polypeptides at the physiological ionic strength (Figure S17 in Supporting Information).…”

“…This choice was predicated on the fact that the polypeptides from the protamine family exhibit extremely high density of the positive charge (due to the incorporation of multiple poly-Arg segments in their sequences), while at the same time lacking any well-defined structure in solution. 42 Analysis of the RVT1/protamine mixture with native MS provides clear evidence that a single antibody molecule readily accommodates up to two protamine polypeptides at the physiological ionic strength (Figure S17 in Supporting Information). No larger complexes (e.g., two antibody molecules cross-linked by a single protamine polypeptide chain) were detected in these measurements, consistent with the small size of these polypeptides, which precludes accommodation of multiple antibodies by a single antigen.…”

Antimicrobial Peptide Recognition Motif of the Substrate Binding Protein SapA from Nontypeable Haemophilus influenzae

“…While NTHi SapA binds human cathelicidin and defensins, SapA homologues from other bacterial species interact with different AMPs. In bactericidal assays with nonpolar sapA knockout strains, SapA contributes to cathelicidin resistance in H. ducreyi (LL-37) and A. pleuropneumoniae (PR-39) and protamine resistance in S. enterica . ,,, PR-39 is a linear proline-rich peptide (net charge +10), while protamine is an arginine-rich AMP with a predicted hairpin loop structure (net charge +21). , Notably, A. pleuropneumoniae is not resistant to beta defensins, and the Sap transporter in H. ducreyi and S. enterica is not involved in resistance to defensins. ,, …”

“…9,11,13,107 PR-39 is a linear prolinerich peptide (net charge +10), while protamine is an arginine-rich AMP with a predicted hairpin loop structure (net charge +21). 11,108 Notably, A. pleuropneumoniae is not resistant to beta defensins, and the Sap transporter in H. ducreyi and S. enterica is not involved in resistance to defensins. 13…”

Effects of histones related to sperm chromatin on embryo development and ART outcomes

“…[5,6] After spermatogenesis, the chromatin of mature sperm has a ring structure that is tightly compacted and resistant to denaturation. [7] The abnormal expression of sperm-specific nuclear proteins or their association with chromatin can alter sperm chromatin structure and affect sperm function. [8,9] In the 6th edition of the WHO manual for human semen analysis, sperm DNA fragmentation, sperm chromatin, sperm aneuploidy, and semen interleukin have been added.…”