Functional insights from structural genomics

Forouhar, F.; Kuzin, A.P.; Seetharaman, J.; Lee, Insun; Zhou, Weihong; Abashidze, M.; Yang, Chen; Wei, Yong; Janjua, H.; Fang, Y.; Wang, Dongyan; Cunningham, K.; Xiao, Rong; Acton, Thomas; Pichersky, Eran; Klessig, Daniel F.; Porter, Carl W.; Montelione, Gaetano T.; Tong, Liang

doi:10.1007/s10969-007-9018-3

Cited by 35 publications

(32 citation statements)

References 50 publications

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“…Some members form pentamers that fit at the vertices of an icosahedral shell, 4 but some other members form hexamers. 4,52 This suggests a probable case of architectural specialization. Given that microcompartments formed the foundations of our search, it was noteworthy to find that the major structural protein from the unrelated, but somewhat analogous case of gas vesicles was identified.…”

Section: Discussionmentioning

confidence: 94%

Exploiting genomic patterns to discover new supramolecular protein assemblies

2008

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Bacterial microcompartments are supramolecular protein assemblies that function as bacterial organelles by compartmentalizing particular enzymes and metabolic intermediates. The outer shells of these microcompartments are assembled from multiple paralogous structural proteins. Because the paralogs are required to assemble together, their genes are often transcribed together from the same operon, giving rise to a distinctive genomic pattern: multiple, typically small, paralogous proteins encoded in close proximity on the bacterial chromosome. To investigate the generality of this pattern in supramolecular assemblies, we employed a comparative genomics approach to search for protein families that show the same kind of genomic pattern as that exhibited by bacterial microcompartments. The results indicate that a variety of large supramolecular assemblies fit the pattern, including bacterial gas vesicles, bacterial pili, and small heat-shock protein complexes. The search also retrieved several widely distributed protein families of presently unknown function. The proteins from one of these families were characterized experimentally and found to show a behavior indicative of supramolecular assembly. We conclude that cotranscribed paralogs are a common feature of diverse supramolecular assemblies, and a useful genomic signature for discovering new kinds of large protein assemblies from genomic data.

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Section: Discussionmentioning

confidence: 94%

Exploiting genomic patterns to discover new supramolecular protein assemblies

2008

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“…However, EutN (which is also related to PduN in sequence) forms hexamers in crystals (22), and recent studies with Halothiobacillus have shown that strains carrying deletions of csoS4-A and csoS4-B form a minority of aberrant structures, suggesting that curvature also can be achieved without the presence of the CsoS4A and CsoS4B proteins (10). Thus, some unanswered questions remain regarding the role of PduN and the mechanism by which curvature is imparted to MCPs.…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis of the Protein Shell of the Microcompartments Involved in Coenzyme B₁₂-Dependent 1,2-Propanediol Degradation bySalmonella

et al. 2011

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Hundreds of bacterial species use microcompartments (MCPs) to optimize metabolic pathways that have toxic or volatile intermediates. MCPs consist of a protein shell encapsulating specific metabolic enzymes. In Salmonella, an MCP is used for 1,2-propanediol utilization (Pdu MCP). The shell of this MCP is composed of eight different types of polypeptides, but their specific functions are uncertain. Here, we individually deleted the eight genes encoding the shell proteins of the Pdu MCP. The effects of each mutation on 1,2-PD degradation and MCP structure were determined by electron microscopy and growth studies. Deletion of the pduBB, pduJ, or pduN gene severely impaired MCP formation, and the observed defects were consistent with roles as facet, edge, or vertex protein, respectively. Metabolite measurements showed that pduA, pduBB, pduJ, or pduN deletion mutants accumulated propionaldehyde to toxic levels during 1,2-PD catabolism, indicating that the integrity of the shell was disrupted. Deletion of the pduK, pduT, or pduU gene did not substantially affect MCP structure or propionaldehyde accumulation, suggesting they are nonessential to MCP formation. However, the pduU or pduT deletion mutants grew more slowly than the wild type on 1,2-PD at saturating B 12 , indicating that they are needed for maximal activity of the 1,2-PD degradative enzymes encased within the MCP shell. Considering recent crystallography studies, this suggests that PduT and PduU may mediate the transport of enzyme substrates/cofactors across the MCP shell. Interestingly, a pduK deletion caused MCP aggregation, suggesting a role in the spatial organization of MCP within the cytoplasm or perhaps in segregation at cell division.

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“…In another case, a conflicting result was initially obtained with regard to a pentamer homolog encoded by the eut operon. The EutN protein was found to be a hexamer in crystals (74). However, later studies showed that EutN was pentameric in solution, suggesting that the hexameric form may have been a minor species that selectively crystallized (75).…”

Section: Pentamers Occupy the Vertices Of The Mcp Shellmentioning

confidence: 99%

“…Initially, the structure of EutN from E. coli was reported as a hexamer at a resolution of 2.7 Å (74). It was then suggested that EutN might distort to fit in the vertices of the Eut MCP and that this distortion could account for the irregular polyhedral shape of Eut MCPs compared to the nearly icosahedral structure of carboxysomes (74). However, a recent report unequivocally demonstrated that EutN is primarily a pentamer in solution by using a technique called oligomeric characterization by addition of charge (9).…”

Section: Shell Proteins Of the Eut Mcpmentioning

confidence: 99%

Diverse Bacterial Microcompartment Organelles

Chowdhury

Sinha

Chun

et al. 2014

Microbiol Mol Biol Rev

214

278

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SUMMARY Bacterial microcompartments (MCPs) are sophisticated protein-based organelles used to optimize metabolic pathways. They consist of metabolic enzymes encapsulated within a protein shell, which creates an ideal environment for catalysis and facilitates the channeling of toxic/volatile intermediates to downstream enzymes. The metabolic processes that require MCPs are diverse and widely distributed and play important roles in global carbon fixation and bacterial pathogenesis. The protein shells of MCPs are thought to selectively control the movement of enzyme cofactors, substrates, and products (including toxic or volatile intermediates) between the MCP interior and the cytoplasm of the cell using both passive electrostatic/steric and dynamic gated mechanisms. Evidence suggests that specialized shell proteins conduct electrons between the cytoplasm and the lumen of the MCP and/or help rebuild damaged iron-sulfur centers in the encapsulated enzymes. The MCP shell is elaborated through a family of small proteins whose structural core is known as a bacterial microcompartment (BMC) domain. BMC domain proteins oligomerize into flat, hexagonally shaped tiles, which assemble into extended protein sheets that form the facets of the shell. Shape complementarity along the edges allows different types of BMC domain proteins to form mixed sheets, while sequence variation provides functional diversification. Recent studies have also revealed targeting sequences that mediate protein encapsulation within MCPs, scaffolding proteins that organize lumen enzymes and the use of private cofactor pools (NAD/H and coenzyme A [HS-CoA]) to facilitate cofactor homeostasis. Although much remains to be learned, our growing understanding of MCPs is providing a basis for bioengineering of protein-based containers for the production of chemicals/pharmaceuticals and for use as molecular delivery vehicles.

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Functional insights from structural genomics

Cited by 35 publications

References 50 publications

Exploiting genomic patterns to discover new supramolecular protein assemblies

Exploiting genomic patterns to discover new supramolecular protein assemblies

Genetic Analysis of the Protein Shell of the Microcompartments Involved in Coenzyme B₁₂-Dependent 1,2-Propanediol Degradation bySalmonella

Diverse Bacterial Microcompartment Organelles

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Functional insights from structural genomics

Cited by 35 publications

References 50 publications

Exploiting genomic patterns to discover new supramolecular protein assemblies

Exploiting genomic patterns to discover new supramolecular protein assemblies

Genetic Analysis of the Protein Shell of the Microcompartments Involved in Coenzyme B12-Dependent 1,2-Propanediol Degradation bySalmonella

Diverse Bacterial Microcompartment Organelles

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Genetic Analysis of the Protein Shell of the Microcompartments Involved in Coenzyme B₁₂-Dependent 1,2-Propanediol Degradation bySalmonella