Structural polymorphism of Methanothermobacter thermautotrophicus MCM

Yen-Ju Chen1, Xiong Yu, Rajesh Kasiviswanathan

  • 1Department of Biochemistry and Molecular Genetics, Box 800733, University Of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.

Insights

Minichromosome maintenance (MCM) proteins are crucial for DNA replication. Studying archaeal MCM revealed large conformational changes, offering insights into yeast MCM activation bypassing phosphorylation.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Minichromosome maintenance (MCM) proteins are vital for DNA replication initiation and elongation in eukaryotes and archaea.
  • Eukaryotes possess six MCM proteins forming complexes believed to unwind DNA, but their mechanism and structure remain unclear.
  • The archaeon Methanothermobacter thermautotrophicus (mtMCM) offers a simpler model system with a single MCM protein.

Purpose of the Study:

  • To investigate the structural dynamics and conformational changes of the mtMCM protein.
  • To understand the mechanism underlying MCM complex function and its regulation, particularly in relation to phosphorylation-dependent activation observed in yeast.

Main Methods:

  • Utilized electron microscopy (EM) and three-dimensional (3D) reconstruction techniques.
  • Examined various fragments of the mtMCM protein, including N-terminal fragments.
  • Compared wild-type mtMCM with a mutant mimicking the yeast MCM5 bob1 mutation.

Main Results:

  • Visualized significant conformational changes within the N-terminal fragment of mtMCM.
  • Observed only subtle structural differences between wild-type and mutated mtMCM via crystal structure analysis, despite the mutation's functional significance in yeast.
  • The study highlights the dynamic nature of MCM proteins.

Conclusions:

  • The observed conformational changes in mtMCM provide new insights into the dynamic behavior of MCM complexes.
  • These findings may explain the phosphorylation-bypass phenotype of the bob1 mutation in yeast, suggesting conformational flexibility is key to MCM activation.
  • Further structural and dynamic studies of MCM proteins are warranted to fully elucidate DNA replication mechanisms.

Related Concept Videos

Hyperthermophilic Bacteria01:21

Hyperthermophilic Bacteria

Domain Bacteria includes some unique hyperthermophilic species. They exhibit remarkable adaptations that enable survival in extreme environments.Thermotoga species are rod-shaped, gram-negative, non-sporulating hyperthermophiles that form a sheath-like envelope called a toga. They ferment sugars or starch, producing lactate, acetate, CO₂, and H₂, and can also grow via anaerobic respiration using H₂ and ferric iron. Found in hot springs and hydrothermal vents, over 20% of their genes show strong...
Diversity of Archaea I01:30

Diversity of Archaea I

Archaea, a domain of single-celled microorganisms, are classified into five major phyla based on genetic and biochemical characteristics: Euryarchaeota, Crenarchaeota, Thaumarchaeota, Korarchaeota, and Nanoarchaeota. Among these, the phylum Euryarchaeota is notable for its remarkable diversity in morphology, metabolism, and ecological adaptations.Morphological and Metabolic DiversityMembers of Euryarchaeota exhibit a variety of cellular shapes, including rods and cocci. Their metabolic pathways...
Anoxygenic Phototrophic Bacteria01:28

Anoxygenic Phototrophic Bacteria

Anoxygenic phototrophic bacteria are a diverse group of microorganisms that perform photosynthesis without producing oxygen. They primarily include purple sulfur bacteria, purple nonsulfur bacteria, green sulfur bacteria, and green nonsulfur bacteria. These bacteria are classified into the Gammaproteobacteria, Alphaproteobacteria, Betaproteobacteria, Chlorobi, and Chloroflexi lineages, each with distinct physiological and ecological adaptations.Purple sulfur bacteria belong to the...
Bacterial Phylum Tenericutes01:24

Bacterial Phylum Tenericutes

The phylum Tenericutes, which includes the single class Mollicutes, comprises bacteria that lack cell walls. The term "Mollicutes" derives from the Latin word mollis, meaning "soft." These organisms are among the smallest known and are commonly referred to as mycoplasmas due to the prominence of the genus Mycoplasma, which includes well-known human pathogens. Despite their inability to stain gram-positively (a result of their lack of cell walls), mycoplasmas are phylogenetically related to the...
Microbial Mats01:25

Microbial Mats

Microbial communities forming biofilms and mats represent complex, spatially structured ecosystems where metabolic processes are stratified according to light, oxygen, and nutrient gradients. Biofilms are initial colonization stages, only a few millimeters thick, while mature microbial mats can reach centimeter-scale thickness and display intricate vertical organization. Their structural and functional heterogeneity allows microorganisms to occupy distinct ecological niches within a few...
Diversity of Archaea IV01:29

Diversity of Archaea IV

Hyperthermophilic archaea are a group of extremophiles thriving at temperatures above 80°C, often in hydrothermal vents and volcanic soils where conditions surpass the boiling point of water. At such temperatures, proteins, membranes, and DNA in most organisms degrade, but hyperthermophiles have evolved remarkable adaptations to maintain stability and function.Unique Cellular FeaturesHyperthermophilic membranes are composed of a monolayer of biphytanyl tetraether lipids, which resist thermal...