Helicasa: Characteristics, Structures And Functions

The  helicase  refers to a group of enzymes of the protein-hydrolytic type that are very important for all living organisms; they are also called motor proteins. These move through the cell cytoplasm, converting chemical energy into mechanical work through ATP hydrolysis.

Its most important function is to break the hydrogen bonds between the nitrogenous bases of nucleic acids, thus allowing their replication. It is important to emphasize that helicases are practically ubiquitous, since they are present in viruses, bacteria and in eukaryotic organisms.

Enzymes involved in the replication of Escherichia coli. Taken and edited from César Benito Jiménez [CC BY-SA 2.5 en (https://creativecommons.org/licenses/by-sa/2.5/es/deed.en)], via Wikimedia Commons.

The first of these proteins or enzymes was discovered in 1976 in the bacterium Escherichia coli ; two years later the first helicase was discovered in a eukaryotic organism, in lily plants.

Currently helicase proteins have been characterized in all natural kingdoms including viruses, which implies that a vast knowledge has been generated about these hydrolytic enzymes, their functions in organisms and their mechanistic role.

Article index

  • one

    Characteristics

    • 1.1

      DNA helicase

    • 1.2

      RNA helicase

  • two

    Taxonomy

    • 2.1

      SF1

    • 2.2

      SF2

    • 23

      SF3

    • 2.4

      SF4

    • 2.5

      SF5

    • 2.6

      SF6

  • 3

    Structure

  • 4

    Features

    • 4.1

      DNA helicase

    • 4.2

      RNA helicase

  • 5

    Medical significance

    • 5.1

      Werner syndrome

    • 5.2

      Bloom syndrome

    • 5.3

      Rothmund-Thomson syndrome

  • 6

    References

Characteristics

Hellicases are biological or natural macromolecules that accelerate chemical reactions (enzymes). They are mainly characterized by separating adenosine triphosphate (ATP) chemical complexes through hydrolysis.

These enzymes use ATP to bind and remodel complexes of deoxyribonucleic acids (DNA) and ribonucleic acids (RNA).

There are at least 2 types of helicases: DNA and RNA.

DNA helicase

DNA helicases act in DNA replication and are characterized by separating double-stranded DNA into single strands.

RNA helicase

These enzymes act in the metabolic processes of ribonucleic acid (RNA) and in ribosomal multiplication, reproduction or biogenesis.

RNA helicase is also key in the pre-splicing process of messenger RNA (mRNA) and the initiation of protein synthesis, after transcription of DNA to RNA in the cell nucleus.

Taxonomy

These enzymes can be differentiated according to their amino acid sequencing homology to the core amino acid ATPase domain, or by shared sequencing motifs. According to the classification, these are grouped into 6 superfamilies (SF 1-6):

SF1

The enzymes of this superfamily have a 3′-5 ′ or 5′-3 ′ translocation polarity and do not form ring structures.

SF2

It is known as the broadest group of helicases and is mainly composed of RNA helicases. They have a translocation polarity generally 3′-5 ′ with very few exceptions.

They have nine motifs (from the English motifs , which translates as “recurring elements”) of highly conserved amino acid sequences and, like SF1, do not form ring structures.

SF3

They are characteristic helicases of viruses and have a unique 3′-5 ‘translocation polarity. They possess only four highly conserved sequence motifs and form ring structures or rings.

SF4

They were first described in bacteria and bacteriophages. They are a group of replicating or replicative helicases.

They have a unique translocation polarity of 5′-3 ′, and have five highly conserved sequence motifs. These helicases are characterized by forming rings.

SF5

They are proteins of the Rho factor type. The helicases of the SF5 superfamily are characteristic of prokaryotic organisms and are hexameric ATP-dependent. They are thought to be closely related to SF4; in addition, they have annular and non-annular shapes.

SF6

They are proteins apparently related to the SF3 superfamily; however, SF6s present a domain of ATPase proteins associated with various cellular activities (AAA proteins) not present in SF3.

Structure

Structurally, all helicases have highly conserved sequence motifs in the anterior portion of their primary structure. A portion of the molecule has a particular amino acid arrangement that depends on the specific function of each helicase.

The most structurally studied helicases are those of the SF1 superfamily. It is known that these proteins are grouped into 2 domains very similar to the multifunctional RecA proteins, and these domains form an ATP binding pocket between them.

Non-conserved regions can have specific domains such as DNA recognition type, cell localization domain, and protein-protein.

Crystal structure of the eIF4A-PDCD4 complex. EIF4A1 dimer of the Helicase subunit, bound to PDCD4 (cyan). Taken and edited from: AyacopPlease flattr this [Public domain or Public domain], from Wikimedia Commons.

Features

DNA helicase

The functions of these proteins depend on an important variety of factors, including environmental stress, cell lineage, genetic background, and stages of the cell cycle.

SF1 DNA helicases are known to serve specific roles in DNA repair, replication, transfer, and recombination.

They separate strands of a DNA double helix and participate in telomere maintenance, double strand break repair, and removal of nucleic acid-associated proteins.

RNA helicase

As mentioned previously, RNA helicases are vital in the vast majority of RNA metabolic processes, and these proteins are also known to participate in the detection of viral RNA.

In addition, they act in the antiviral immune response, since they detect foreign RNA or foreign to the body (in vertebrates).

Medical significance

Hellicases help cells overcome endogenous and exogenous stress, avoiding chromosomal instability and maintaining cellular balance.

The failure of this system or homeostatic equilibrium is related to genetic mutations that involve genes that encode proteins of the helicase type; for this reason they are the subject of biomedical and genetic studies.

Below we will mention some of the diseases related to mutations in genes that encode DNA as helicase-type proteins:

Werner syndrome

It is a genetic disease caused by a mutation in a gene called WRN, which encodes a helicase. The mutant helicase does not work properly and causes a number of diseases that together make up Werner syndrome.

The main characteristic of those who suffer from this pathology is their premature aging. For the disease to manifest itself, the mutant gene must be inherited from both parents; its incidence is very low and there is no treatment for its cure.

Bloom syndrome

Bloom syndrome is a genetic disease caused by the mutation of an autosomal gene called BLM that encodes a helicase protein. It only occurs for individuals homozygous for that character (recessive).

The main characteristic of this rare disease is hypersensitivity to sunlight, which causes skin lesions of the erythromatous rash. There is no cure yet.

Rothmund-Thomson syndrome

It is also known as congenital atrophic poikiloderma. It is a very rare disease of genetic origin: to date there are less than 300 cases described worldwide. 

It is caused by a mutation in the RECQ4 gene, an autosomal recessive gene that is located on chromosome 8.

Symptoms or conditions of this syndrome include juvenile cataracts, abnormalities in the skeletal system, depigmentation, capillary dilation, and atrophy of the skin (poikiloderma). In some cases, hyperthyroidism and deficiency in testosterone production may occur.

References

  1. RM Brosh (2013). DNA helicases involved in DNA repair and their roles in cancer. Nature Reviews Cancer.
  2. Helicase. Recovered from nature.com.
  3. Helicase. Recovered from en.wikipedia.org.
  4. A. Juárez, LP Islas, AM Rivera, SE Tellez, MA Duran (2011). Rothmund-Thompson syndrome (congenital atrophic poikiloderma) in a pregnant woman. Clinic and Research in Gynecology and Obstetrics.
  5. KD Raney, AK Byrd, S. Aarattuthodiyil (2013). Structure and Mechanisms of SF1 DNA Helicases. Advances in Experimental Medicine and Biology.
  6. Bloom syndrome. Recovered from Medicina.ufm.edu.
  7. M. Singleton, MS Dillingham, DB Wigley (2007). Structure and mechanism of Helicases and Nucleic Acid Translocases. Annual Review of Biochemistry.

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