Protamines, in the Footsteps of Linker Histone Evolution

Abstract

It was perhaps a lucky coincidence that the early attempts to establish the chemical composition of the cell nucleus were initially carried out on such diverse biological systems as salmon sperm heads (1) and geese and chicken erythrocytes (2). Examination of sperm and erythrocyte systems, respectively, lead to the protamine and histone concepts (3). We know with certainty that, with the exception of the male gametes, all somatic cells exclusively contain histones. Hence, in metazoans, protamines (4, 5) are confined to the sperm nuclear chromatin, and even among sperm, protamines are not always present. Indeed, a large number of metazoans contain somatic-like histones in their sperm, and some crustaceans (order Decapoda) lack any chromosomal proteins in their sperm (6, 7). Therefore, in contrast to the somatic nucleus, sperm chromatin may have a much more diverse protein composition. It was not until the first attempt of classification of the sperm nuclear basic proteins (SNBPs) 2 by David Bloch (6,8), an effort later on extended by Harold Kasinsky (7), that a clearer picture started to emerge in this regard.More recently, an enormous effort has been carried out in several laboratories, including our own (9 -15), to extend this analysis to a large number of representative organisms from the different phylogenetic groups. With a broader perspective now available, SNBP heterogeneity can be restricted to three major groups or types: histone (H), protamine (P), and protamine-like (PL) (16).Histones consist of core histones (histones H2A, H2B, H3, and H4) and linker histones (histone H1 family). The names refer to the structural role of these proteins. Core histones are responsible for constraining DNA wrapped about a histone core to produce a nucleoprotein complex (chromatin subunit) known as a nucleosome core particle. Linker histones bind to the linker DNA regions connecting adjacent nucleosome core particles and assist in the folding of the chromatin fiber (17).Protamines are a highly compositionally and structurally heterogeneous group of proteins (9). They exhibit a high charge density and a prevalence of arginine in their composition (13), a fact that it is most likely related to the higher affinity with which this basic amino acid binds to DNA (18). They lack any secondary structure in solution but may adopt a folded conformation upon interaction with DNA. Protamine-like proteins share compositional and structural similarities between histones and protamines (9, 16). Hence they represent a structurally intermediate group that will be discussed more extensively in the following sections of this review.To a certain extent, all three types of SNBP can be considered structurally analogous as all of them produce folded chromatin fibers of 30 -50 nm (19) regardless of the particular structure of the individual nucleoprotamine complexes. At the functional level, somatic histones bind to DNA in a highly dynamic way that not only helps in the folding of the genome but also has an important role in the epigenetic reg...

Origin and evolution of chromosomal sperm proteins

“…This is especially evident in mammals where 11 different linker histones have been identified (see (13) for review). In contrast to core histones, whose origin can be traced back to archaebacteria, (37) the evolutionary origin of histone H1 appears to have occurred early in eubacteria.…”

“…(10,11) The term ''protamine-like'' was first described by Subirana. (12) The PL-type of SNBPs represent a structurally and functionally intermediate group between the H-and P-type SNBPs that are related to histone H1 (1,13,14) (Fig. 1A, B).…”

Tissue heterogeneity of the mammalian mitochondrial proteome

“…Mitochondrial DNA (mtDNA) can form nucleoids with structure similar to chromatin in plants (13), and the yeast literature has demonstrated that histone family proteins are important in proper mitochondrial function (7,9,11). There are also evolutionary correlates of histone-like proteins that are important in DNA structure in the prokaryotic organisms that are thought to represent the predecessors of mitochondria (15,19,22). The electron micrographs of the mitochondrial nucleoid demonstrate a tightly wound ball of DNA (13) with protein associated, whereas proteins similar to the yeast histone HM protein have been isolated in bovine heart mitochondrial preparations (34).…”

Functional equivalence of HMGA- and histone H1-like domains in a bacterial transcriptional factor

“…5A). In C7, the AT-hooks are replaced by the 102-residue, R-rich human protamine 2 (Prt2; theoretical pI ϭ 11.9), which lacks a defined structure and binds DNA in vitro like H1 CTR but with higher affinity (27,28). In C8, the AT-hooks are replaced by the 105-residue human cytochrome C (CytC; theoretical pI ϭ 9.58), which has defined structure and can bind DNA because of its positive charge although it is not a proper DNAbinding protein (29).…”