Protamines

Protamines are low molecular weight basic proteins in the sperm nuclei of most animal groups. They make up a fraction of the main protein in mature sperm of fish .

Content

Function

Protamines serve to organize chromatin in the sperm nuclei , replacing histones in it.

In the nuclei of somatic cells and egg cells, DNA is associated with histones . Chromatin of sperm precursors, spermatogonia , contains the main histones associated with acid DNA, but during spermatogenesis at the spermatid stage, histones are removed from the nucleus and the DNA binds to protamines to form nucleoprotamines .

This allows condensing chromatin to be much denser and reducing the size of the sperm nucleus. Unlike chromatin with the participation of histones, chromatin with the participation of protamines is inactive - transcription processes are impossible in the sperm nucleus.

Composition and species diversity of protamines

The molecular weight of protamines is 4-12 KDa , fish protamines contain up to 35 amino acid residues, bird and mammalian protamines - most often 50-60 amino acid residues. Invertebrate protamines are still poorly understood, but it is known that mollusk protamines, in contrast to vertebrate protamines, which contain a large amount (up to 90% in some fish) of arginine, also contain a significant amount of lysine . A specific feature of the mammalian protamine composition is a rather high cysteine content (with an arginine content of 47-61%), which leads to the formation of disulfide bridges with crosslinking of monomeric protamines.

In bony fish, protamines are represented by a large number of forms - for example, six different protamines with a close amino acid sequence were found in trout .

The sperm protamines of most mammalian species are represented by a single P1 form, ranging in length from 35 ( Semnopithecus priam monkey) to 69 ( Pseudochirops cupreus posum ) amino acid residues ^[1] , the only exception at present are humans and mice, in which protamine forms are synthesized - short P1 ( 51 amino acid residues in both species) and long P2 (102 and 107 residues, respectively). Protamine P2 of both humans and mice undergoes post-translational modification , splitting into fragments ^[2] ^, ^[3] with their subsequent crosslinking by disulfide bridges to cysteine residues.

At the same time, almost all mammals have both genes encoding the protamines P1 and P2, but the P2 gene is weakly expressed ^[4]

Amino acid sequence of human protamine P1 ^[5]

  10 20 30 40 50
 MARYRCCRSQ SRSRYYRQRQ RSRRRRRRSC QTRRRAMRCC RPRYRPRCRR 
 H

Disulfide bridges:

Intramolecular: 40 - 48
Intermolecular: 6, 39

Amino acid sequence of human protamine P2 ^[6]

  10 20 30 40 50
 MVRYRVRSLS ERSHEVYRQQ LHGQEQGHHG QEEQGLSPEH VEVYERTHGQ 
         60 70 80 90 100
 SHYRRRHCSR RRLHRIHRRQ HRSCRRRKRR SCRHRRRHRR GCRTRKRTCR 
 Rh

Properties

It is highly soluble in water, acidic and neutral.
Precipitated with alkalis .
No denaturation when heated.
Form salts with acids and complexes with acidic proteins.

Pharmacological use

To slow down the absorption of insulin , it is mixed with a sparingly soluble complex of protamines (the name is called Hagedorn's neutral protamine , denoted by the abbreviation "NPH" or "NPH" in the name).
Protamine sulfate serves as an antidote when using heparin as a drug with anticoagulant ( anticoagulant ) action. 1 mg of protamine sulfate neutralizes 100 IU of heparin. On average, neutralization occurs within 5 minutes after an intravenous injection of protamine sulfate.

Literature

Balhorn R. The protamine family of sperm nuclear proteins // Genome Biol. 2007; V.8. N.9. P.227. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375014/

Notes

↑ protamine P1 search // Uniprot
↑ Yoshii, T. Fine resolution of human sperm nucleoproteins by two-dimensional electrophoresis (English) // Molecular Human Reproduction : journal. - 2005 .-- 11 October ( vol. 11 , no. 9 ). - P. 677-681 . - ISSN 1460-2407 1360-9947, 1460-2407 . - DOI : 10.1093 / molehr / gah217 .
↑ Carre-Eusebe, D .; Lederer, F .; Le, KHD; Elsevier, SM Processing of the precursor of protamine P2 in mouse. Peptide mapping and N-terminal sequence analysis of intermediates (English) // Biochemical journal : journal. - 1991. - Vol. 277 , no. 1 . - P. 39-45 .
↑ Urich, Klaus. Comparative Animal Biochemistry. - Springer Science & Business Media, 2013-04-17. - P. 33-34. - ISBN 978-3-662-06303-3 .
↑ HSP1_HUMAN Sperm protamine P1 // Uniprot
↑ PRM2_HUMAN // Uniprot

[1] rotamine P1 search // Uniprot

[2] Yoshii, T. Fine resolution of human sperm nucleoproteins by two-dimensional electrophoresis (English) // Molecular Human Reproduction : journal. - 2005 .-- 11 October ( vol. 11 , no. 9 ). - P. 677-681 . - ISSN 1460-2407 1360-9947, 1460-2407 . - DOI : 10.1093 / molehr / gah217 .

[3] Carre-Eusebe, D .; Lederer, F .; Le, KHD; Elsevier, SM Processing of the precursor of protamine P2 in mouse. Peptide mapping and N-terminal sequence analysis of intermediates (English) // Biochemical journal : journal. - 1991. - Vol. 277 , no. 1 . - P. 39-45 .

[4] Urich, Klaus. Comparative Animal Biochemistry. - Springer Science & Business Media, 2013-04-17. - P. 33-34. - ISBN 978-3-662-06303-3 .

[5] HSP1_HUMAN Sperm protamine P1 // Uniprot

[6] PRM2_HUMAN // Uniprot