XOL-1 Switch protein N-terminal domain

Last updated
Xol-1_N

PDB 1mg7 EBI.jpg

crystal structure of xol-1
Identifiers
Symbol Xol-1_N
Pfam PF09108
Pfam clan CL0329
InterPro IPR015192
SCOP 1mg7
SUPERFAMILY 1mg7

In molecular biology, Xol-1 is a protein domain, also named the Switch protein, is essentially a sex-determining protein. This entry focuses on the N-terminal domain of Xol-1. Xol-1, the master switch gene controlling sex-determination system and dosage compensation. This protein is normally expressed in males, where it promotes male development and prevents dosage compensation. [1]

Protein domain

A protein domain is a conserved part of a given protein sequence and (tertiary) structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural domains. One domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeric proteins.

Sex-determination system A biological system that determines the development of sexual characteristics in an organism

A sex-determination system is a biological system that determines the development of sexual characteristics in an organism. Most organisms that create their offspring using sexual reproduction have two sexes. Occasionally, there are hermaphrodites in place of one or both sexes. There are also some species that are only one sex due to parthenogenesis, the act of a female reproducing without fertilization.

A dose is a measured quantity of a medicine, nutrient, or pathogen which is delivered as a unit. The greater the quantity delivered, the larger the dose. Doses are most commonly measured for compounds in medicine. The term is usually applied to the quantity of a drug or other agent administered for therapeutic purposes, but may be used to describe any case where a substance is introduced to the body. In nutrition, the term is usually applied to how much of a specific nutrient is in a person's diet or in a particular food, meal, or dietary supplement. For bacterial or viral agents, dose typically refers to the amount of the pathogen required to infect a host. For information on dosage of toxic substances, see Toxicology. For information on excessive intake of pharmaceutical agents, see Drug overdose.

Contents

Function

The function of the Xol-1 protein is to act as a primary sex-determining factor that promotes sexual differentiation. It is required for proper sexual differentiation and male viability. High expression during gastrulation triggers male development, while low expression at that time triggers hermaphrodite development. Although related to GHMP kinase, its mode of action remains unclear. [2]

Gastrulation Phase in the early embryonic development of most animals.

Gastrulation is a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a multilayered structure known as the gastrula. Before gastrulation, the embryo is a continuous epithelial sheet of cells; by the end of gastrulation, the embryo has begun differentiation to establish distinct cell lineages, set up the basic axes of the body, and internalized one or more cell types including the prospective gut.

Hermaphrodite organism with both male and female reproductive organs

In biology, a hermaphrodite is an organism that has complete or partial reproductive organs and produces gametes normally associated with both male and female sexes. Many taxonomic groups of animals do not have separate sexes. In these groups, hermaphroditism is a normal condition, enabling a form of sexual reproduction in which either partner can act as the "female" or "male." For example, the great majority of tunicates, pulmonate snails, opisthobranch snails, earthworms and slugs are hermaphrodites. Hermaphroditism is also found in some fish species and to a lesser degree in other vertebrates. Most plants are also hermaphrodites.

Structure

The protein adopts a secondary structure consisting of five alpha helices and six antiparallel beta sheets. The fold of this family is similar to that found in ribosomal protein S5 domain 2-like. [2] The active site of the enzyme is found at the interface between this domain and the C-terminal GHMP-like domain.

Alpha helix type of secondary structure

The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-spiral conformation in which every backbone N−H group donates a hydrogen bond to the backbone C=O group of the amino acid located three or four residues earlier along the protein sequence.

In biochemistry, two biopolymers are antiparallel if they run parallel to each other but with opposite directionality (alignments). An example is the two complementary strands of a DNA double helix, which run in opposite directions alongside each other.

Protein folding the process of assisting in the covalent and noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure

Protein folding is the physical process by which a protein chain acquires its native 3-dimensional structure, a conformation that is usually biologically functional, in an expeditious and reproducible manner. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil. Each protein exists as an unfolded polypeptide or random coil when translated from a sequence of mRNA to a linear chain of amino acids. This polypeptide lacks any stable (long-lasting) three-dimensional structure. As the polypeptide chain is being synthesized by a ribosome, the linear chain begins to fold into its three-dimensional structure. Folding begins to occur even during translation of the polypeptide chain. Amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein, known as the native state. The resulting three-dimensional structure is determined by the amino acid sequence or primary structure.

Related Research Articles

Testis-determining factor protein-coding gene in the species Homo sapiens

Testis-determining factor (TDF), also known as sex-determining region Y (SRY) protein, is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in humans. SRY is an intronless sex-determining gene on the Y chromosome in therians ; mutations in this gene lead to a range of disorders of sex development (DSD) with varying effects on an individual's phenotype and genotype.

Dosage compensation Compensating for the variation in the unpaired sex chromosome:autosome chromosome ratios between sexes by activation or inactivation of genes on one or both of the sex chromosomes.

Dosage compensation is the process by which organisms equalize the expression of genes between members of different biological sexes. Across species, different sexes are often characterized by different types and numbers of sex chromosomes. In order to neutralize the large difference in gene dosage produced by differing numbers of sex chromosomes among the sexes, various evolutionary branches have acquired various methods to equalize gene expression among the sexes. Because sex chromosomes contain different numbers of genes, different species of organisms have developed different mechanisms to cope with this inequality. Replicating the actual gene is impossible; thus organisms instead equalize the expression from each gene. For example, in humans, females (XX) silence the transcription of one X chromosome of each pair, and transcribe all information from the other, expressed X chromosome. Thus, human females have the same number of expressed X-linked genes as do human males (XY), both sexes having essentially one X chromosome per cell, from which to transcribe and express genes.

ZW sex-determination system chromosomal system that determines the sex of offspring in birds, some fish and crustaceans such as the giant river prawn, some insects (including butterflies and moths), and some reptiles, including Komodo dragons

The ZW sex-determination system is a chromosomal system that determines the sex of offspring in birds, some fish and crustaceans such as the giant river prawn, some insects, and some reptiles, including Komodo dragons. The letters Z and W are used to distinguish this system from the XY sex-determination system.

CCAAT-enhancer-binding proteins

CCAAT-enhancer-binding proteins is a family of transcription factors composed of six members, named from C/EBPα to C/EBPζ. They promote the expression of certain genes through interaction with their promoters. Once bound to DNA, C/EBPs can recruit so-called co-activators that in turn can open up chromatin structure or recruit basal transcription factors.

c-Jun N-terminal kinases

c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock. They also play a role in T cell differentiation and the cellular apoptosis pathway. Activation occurs through a dual phosphorylation of threonine (Thr) and tyrosine (Tyr) residues within a Thr-Pro-Tyr motif located in kinase subdomain VIII. Activation is carried out by two MAP kinase kinases, MKK4 and MKK7, and JNK can be inactivated by Ser/Thr and Tyr protein phosphatases. It has been suggested that this signaling pathway contributes to inflammatory responses in mammals and insects.

Mitogen-activated protein kinase 9 protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 9 is an enzyme that in humans is encoded by the MAPK9 gene.

Mef2

In the field of molecular biology, myocyte enhancer factor-2 (Mef2) proteins are a family of transcription factors which through control of gene expression are important regulators of cellular differentiation and consequently play a critical role in embryonic development. In adult organisms, Mef2 proteins mediate the stress response in some tissues. Mef2 proteins contain both MADS-box and Mef2 DNA-binding domains.

Steroidogenic factor 1 protein-coding gene in the species Homo sapiens

The steroidogenic factor 1 (SF-1) protein is a transcription factor involved in sex determination by controlling activity of genes related to the reproductive glands or gonads and adrenal glands. This protein is encoded by the NR5A1 gene, a member of the nuclear receptor subfamily, located on the long arm of chromosome 9 at position 33.3. It was originally identified as a regulator of genes encoding cytochrome P450 steroid hydroxylases, however, further roles in endocrine function have since been discovered.

ATF4 protein-coding gene in the species Homo sapiens

Activating transcription factor 4 , also known as ATF4, is a protein that in humans is encoded by the ATF4 gene.

SOX9 protein-coding gene in the species Homo sapiens

Transcription factor SOX-9 is a protein that in humans is encoded by the SOX9 gene.

HES1 protein-coding gene in the species Homo sapiens

Transcription factor HES1 is a protein that is encoded by the Hes1 gene, and is the mammalian homolog of the hairy gene in Drosophila. HES1 is one of the seven members of the Hes gene family (HES1-7). Hes genes code nuclear proteins that suppress transcription.

RFX1 protein-coding gene in the species Homo sapiens

MHC class II regulatory factor RFX1 is a protein that, in humans, is encoded by the RFX1 gene located on the short arm of chromosome 19.

FGF9 protein-coding gene in the species Homo sapiens

Glia-activating factor is a protein that in humans is encoded by the FGF9 gene.

POU4F1 protein-coding gene in the species Homo sapiens

POU domain, class 4, transcription factor 1 (POU4F1) also known as brain-specific homeobox/POU domain protein 3A (BRN3A), homeobox/POU domain protein RDC-1 or Oct-T1 is a protein that in humans is encoded by the POU4F1 gene.

HAND1 protein-coding gene in the species Homo sapiens

Heart- and neural crest derivatives-expressed protein 1 is a protein that in humans is encoded by the HAND1 gene.

DMRT1 protein-coding gene in the species Homo sapiens

Doublesex and mab-3 related transcription factor 1, also known as DMRT1, is a protein which in humans is encoded by the DMRT1 gene.

SOX12 protein-coding gene in the species Homo sapiens

SOX12 is a protein that in humans is encoded by the SOX12 gene. Sox12 belongs to the SoxC group of Sox family of transcription factors, together with Sox4 and Sox11. Sox12-null knockout mice appear normal, unlike Sox4 or Sox11 knockout mice. This probably comes from functional redundancy with Sox4 and Sox11. Sox12 is a weaker activator than both Sox4 and Sox11 in mouse.

DM domain

In molecular biology the DM domain is a protein domain first discovered in the doublesex proteins of Drosophila melanogaster and is also seen in proteins from Caenorhabditis elegans. In D. melanogaster the doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. These proteins are believed to function as transcription factors on downstream sex-determination genes, especially on neuroblast differentiation and yolk protein genes transcription. The DM domain binds DNA as a dimer, allowing the recognition of pseudopalindromic sequences. The NMR analysis of the DSX DM domain revealed a novel zinc module containing 'intertwined' CCHC and HCCC zinc-binding sites. The recognition of the DNA requires the carboxy-terminal basic tail which contacts the minor groove of the target sequence.

SoxC group is group C of Sry-related HMG box proteins transcription factors. SoxC genes play an important role in determining the cell fate of neuronal mesenchymal progenitor cells in many developmental processes.

References

  1. ↑ Hargitai B, Kutnyánszky V, Blauwkamp TA, Steták A, Csankovszki G, Takács-Vellai K, et al. (2009). "xol-1, the master sex-switch gene in C. elegans, is a transcriptional target of the terminal sex-determining factor TRA-1". Development. 136 (23): 3881–7. doi:10.1242/dev.034637. PMC   2778738  Lock-green.svg. PMID   19906855.
  2. 1 2 Luz JG, Hassig CA, Pickle C, Godzik A, Meyer BJ, Wilson IA (2003). "XOL-1, primary determinant of sexual fate in C. elegans, is a GHMP kinase family member and a structural prototype for a class of developmental regulators". Genes Dev. 17 (8): 977–90. doi:10.1101/gad.1082303. PMC   196039  Lock-green.svg. PMID   12672694.

This article incorporates text from the public domain Pfam and InterPro IPR015192

The public domain consists of all the creative works to which no exclusive intellectual property rights apply. Those rights may have expired, been forfeited, expressly waived, or may be inapplicable.

Pfam Database of protein families

Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models. The most recent version, Pfam 31.0, was released in March 2017 and contains 16,712 families.

InterPro is a database of protein families, domains and functional sites in which identifiable features found in known proteins can be applied to new protein sequences in order to functionally characterise them.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.