COFACTOR: improved protein function prediction by combining structure, sequence and protein–protein interaction information

Zhang, Chengxin; Freddolino, Peter L.; Zhang, Yang

doi:10.1093/nar/gkx366

Cited by 486 publications

(430 citation statements)

References 39 publications

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“…The identified PVF proteins were annotated using BLASTp against the NCBI non‐reductant (nr) database with an E ‐value threshold of 10 −5 and InterProScan 5 under default settings for Gene Ontology (GO). Proteins without GO annotation were further searched against COFACTOR, which derives protein function based on structural comparisons and protein–protein networks, using the I‐TASSER server with a GO‐score threshold of 0.5 . In addition, a BLASTp search with E ‐value threshold of 10 −5 was conducted to compare the PVF composition between P. diffusa and three other ampullariids .…”

Section: Methodsmentioning

confidence: 99%

Egg perivitelline fluid proteome of a freshwater snail: Insight into the transition from aquatic to terrestrial egg deposition

Zhang

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale Proteins from the egg perivitelline fluid (PVF) are assumed to play critical roles in embryonic development, but for many groups of animals their identities remain unknown. Identifying egg PVF proteins is a critical step towards understanding their functions including their roles in evolutionary transition in habitats. Methods We applied proteomic and transcriptomic analysis to investigate the PVF proteome of the eggs of Pomacea diffusa, an aerial ovipositing freshwater snail in the family Ampullariidae. The PVF proteins were separated with the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) method, and proteomic analysis was conducted using an LTQ Velos ion trap mass spectrometer coupled with liquid chromatography. Comparison of PVF proteomes and evolution analyses was performed between P. diffusa and other ampullariids. Results In total, 32 egg PVF proteins were identified from P. diffusa. They were categorized as PV1‐like subunits, immune‐responsive proteins, protein degradation, signaling and binding, transcription and translation, metabolism, oxidation–reduction and proteins with unknown function. Interestingly, the proteome includes a calcium‐binding protein important in forming the hard eggshell that enabled the terrestrial transition. However, it does not include PV2, a neurotoxic protein that was assumed to be present in all Pomacea species. Conclusions The PVF proteome data from P. diffusa can help us better understand the roles that reproductive proteins played during the transition from underwater to terrestrial egg deposition. Moreover, they could be useful in comparative studies of the terrestrialization in several groups of animals that occurred independently during their evolution.

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Section: Methodsmentioning

confidence: 99%

Egg perivitelline fluid proteome of a freshwater snail: Insight into the transition from aquatic to terrestrial egg deposition

Zhang

et al. 2020

Rapid Comm Mass Spectrometry

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“…The first information necessary is the alignment of the target protein. Then the target protein structure is stripped of the sequence and redesigned using the protein package ViPS available online . At this point, the user will have two lists of aligned proteins one natural and the other artificial.…”

Section: Resultsmentioning

confidence: 99%

Identification of Protein Functional Regions

et al. 2020

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Protein sequence stores the information relative to both functionality and stability, thus making it difficult to disentangle the two contributions. However, the identification of critical residues for function and stability has important implications for the mapping of the proteome interactions, as well as for many pharmaceutical applications, e. g. the identification of ligand binding regions for targeted pharmaceutical protein design. In this work, we propose a computational method to identify critical residues for protein functionality and stability and to further categorise them in strictly functional, structural and intermediate. We evaluate single site conservation and use Direct Coupling Analysis (DCA) to identify co‐evolved residues both in natural and artificial evolution processes. We reproduce artificial evolution using protein design and base our approach on the hypothesis that artificial evolution in the absence of any functional constraint would exclusively lead to site conservation and co‐evolution events of the structural type. Conversely, natural evolution intrinsically embeds both functional and structural information. By comparing the lists of conserved and co‐evolved residues, outcomes of the analysis on natural and artificial evolution, we identify the functional residues without the need of any a priori knowledge of the biological role of the analysed protein.

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“…These previously identified protein-protein interactions may be relevant for the regulation of mycobacterial TopoI activity. However, experimental data on protein-protein interactions of mycobacterial TopoI that may inform on the physiological setting of its function 37 is currently not available. In this study, we tried to identify such potential partners present in the total soluble proteins of M. smegmatis using the approaches of Co-IP and pull-down assays coupled to mass spectrometry.…”

Section: Discussionmentioning

confidence: 99%

Distinct Mechanism Evolved for Mycobacterial RNA Polymerase and Topoisomerase I Protein–Protein Interaction

Banda

Cao

Tse‐Dinh

2017

Journal of Molecular Biology

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We report here a distinct mechanism of interaction between topoisomerase I and RNA polymerase in Mycobacterium tuberculosis and Mycobacterium smegmatis that has evolved independently from the previously characterized interaction between bacterial topoisomerase I and RNA polymerase. Bacterial DNA topoisomerase I is responsible for preventing the hyper-negative supercoiling of genomic DNA. The association of topoisomerase I with RNA polymerase during transcription elongation could efficiently relieve transcription-driven negative supercoiling. Our results demonstrate a direct physical interaction between the C-terminal domains of topoisomerase I (TopoI-CTD) and the β′ subunit of RNA polymerase of M. smegmatis in the absence of DNA. The TopoI-CTD in mycobacteria are evolutionarily unrelated in amino acid sequence and three-dimensional structure to the TopoI-CTD found in the majority of bacterial species outside Actinobacteria, including Escherichia coli. The functional interaction between topoisomerase I and RNA polymerase has evolved independently in mycobacteria and E. coli, with distinctively different structural elements of TopoI-CTD utilized for this protein-protein interaction. Zinc ribbon motifs in E. coli TopoI-CTD are involved in the interaction with RNA polymerase. For M. smegmatis TopoI-CTD, a 27 amino acid tail that is rich in basic residues at the C-terminal end is responsible for the interaction with RNA polymerase. Overexpression of recombinant TopoI-CTD in M. smegmatis competed with the endogenous topoisomerase I for protein-protein interactions with RNA polymerase. The TopoI-CTD overexpression resulted in decreased survival following treatment with antibiotics and hydrogen peroxide, supporting the importance of the protein-protein interaction between topoisomerase I and RNA polymerase during stress response of mycobacteria.

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COFACTOR: improved protein function prediction by combining structure, sequence and protein–protein interaction information

Cited by 486 publications

References 39 publications

Egg perivitelline fluid proteome of a freshwater snail: Insight into the transition from aquatic to terrestrial egg deposition

Egg perivitelline fluid proteome of a freshwater snail: Insight into the transition from aquatic to terrestrial egg deposition

Identification of Protein Functional Regions

Distinct Mechanism Evolved for Mycobacterial RNA Polymerase and Topoisomerase I Protein–Protein Interaction

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