Temperature‐Dependent Molecular Adaptations, Microbial Proteins

Kumar, Sandeep; Singh, Satish K.; Gromiha, M. Michael

doi:10.1002/9780470054581.eib516

Cited by 8 publications

(9 citation statements)

References 157 publications

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“…On the practical side, comparison of aggregation between extremophiles and mesophiles could suggest design and formulation strategies to mitigate aggregation in biotherapeutics. This is because several conditions encountered during manufacture, purification, packaging, storage, and shipping of these drug products are similar to the environmental conditions faced by the proteins from extremophiles 73. Hence, the degradation issues that occur during the development of these drug products are similar to the challenges faced by the extremophilic proteins in the ambient environments of the source organisms 73.…”

Section: Discussionmentioning

confidence: 99%

“…This is because several conditions encountered during manufacture, purification, packaging, storage, and shipping of these drug products are similar to the environmental conditions faced by the proteins from extremophiles 73. Hence, the degradation issues that occur during the development of these drug products are similar to the challenges faced by the extremophilic proteins in the ambient environments of the source organisms 73. The formulation scientists and extremophilic organisms, both ultimately aspire toward the same goal.…”

Section: Discussionmentioning

confidence: 99%

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How do thermophilic proteins resist aggregation?

Thangakani¹,

Kumar²,

Velmurugan³

et al. 2012

Proteins

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Aggregation is an ancient threat that must be overcome by proteins from all organisms to maintain their native functional states. This is essential for the maintenance of metabolic flux and viability of their cellular machineries. Here, we compare the aggregation-resistance strategies adapted by the thermophilic proteins and their mesophilic homologs using a dataset of 373 protein families. Like their mesophilic homologs, the thermophilic protein sequences also contain potential aggregation prone regions (APRs), capable of forming cross-β motif and amyloid-like fibrils. Tetrapeptide and hexapeptide amyloid-like fibril forming sequence patterns and experimentally proven amyloid-like fibril forming peptide sequences were also detected in the thermophilic proteins. Both the thermophilic and the mesophilic proteins use similar strategies to resist aggregation. However, the thermophilic proteins show superior utilization of these strategies. The thermophilic protein monomers show greater ability to "stow away" the APRs in the hydrophobic cores to protect them from solvent exposure. The thermophilic proteins are also better at gatekeeping the APRs by surrounding them with charged residues (Asp, Glu, Lys, and Arg) and Pro to a greater extent. While thermophilic and mesophilic proteins in our dataset are highly homologous and show strong overall sequence conservation, the APRs are not conserved between the homologs. These findings indicate that evolution is working to avoid amyloidogenic regions in proteins. Our results are also consistent with the observation that thermophilic cells often accumulate small molecule osmolytes capable of stabilizing their proteins and other macromolecules. This study has important implications for rational design and formulation of therapeutic proteins and antibodies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

How do thermophilic proteins resist aggregation?

Thangakani¹,

Kumar²,

Velmurugan³

et al. 2012

Proteins

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“…From the perspective of product development, it is the molecular characteristics of the product that are important and can be controlled (4,7,10,12,14). Even humanized and fully human mAbs may show immunogenicity in the clinic.…”

Section: Aggregation and Immunogenicity Issues In Biotherapeuticsmentioning

confidence: 99%

Coupling of Aggregation and Immunogenicity in Biotherapeutics: T- and B-Cell Immune Epitopes May Contain Aggregation-Prone Regions

et al. 2011

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Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregation prone regions as well as T- and B-cell immune epitopes from protein sequence and structure have become available recently. Here, we describe a potential coupling between aggregation and immunogenicity: T-cell and B-cell immune epitopes in therapeutic proteins may contain aggregation-prone regions. The details of biological mechanisms behind this observation remain to be understood. However, our observation opens up an exciting potential for rational design of de-immunized novel, as well as follow on biotherapeutics with reduced aggregation propensity.

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“…More recently, Panja et al statistically explored the changes in microbial proteins adapted to different types of environments, and they diverged both in terms of amino acid composition and in their arrangement [81], a result in line with the weak selection concept [82]. According to these and other previous results, salinity, pH and temperature would represent the major environmental drivers of how proteins evolve [4,[83][84][85],…”

Section: How the Environment Constrains Microbial Protein Diversifica...mentioning

confidence: 78%

Quantifying Microbial Guilds

Rivas-Santisteban

Yubero

Robaina-Estévez

et al. 2023

Preprint

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The ecological role of microorganisms is of utmost importance due to their multiple interactions with the environment. However, assessing the contribution of individual taxonomic groups has proven difficult despite the availability of high throughput data, hindering our understanding of such complex systems. Here, we propose a quantitative definition of guild that is readily applicable to metagenomic data. Our framework focuses on the functional character of protein sequences, as well as their diversifying nature. First, we discriminate functional sequences from the whole sequence space corresponding to a gene annotation to then quantify their contribution to the guild composition across environments. In addition, we distinguish between sequence spaces that have different ways of carrying out the function. We demonstrate the validity of our approach by quantifying the guild of ammonia oxidation, and further reveal novel ecological dynamics of putrescine uptake guild in marine ecosystems. Thus, guilds help elucidate the functional role of different taxonomic groups with profound implications in the study of microbial communities.

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Temperature‐Dependent Molecular Adaptations, Microbial Proteins

Cited by 8 publications

References 157 publications

How do thermophilic proteins resist aggregation?

How do thermophilic proteins resist aggregation?

Coupling of Aggregation and Immunogenicity in Biotherapeutics: T- and B-Cell Immune Epitopes May Contain Aggregation-Prone Regions

Quantifying Microbial Guilds

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