4.0 Article

An automated stochastic approach to the identification of the protein specificity determinants and functional subfamilies

Journal

ALGORITHMS FOR MOLECULAR BIOLOGY
Volume 5, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/1748-7188-5-29

Keywords

-

Funding

  1. EMBO [ALTF 2007-119]
  2. Russian Foundation for Basic Research [09-04-92742, 09-04-92745, 10-04-00431]
  3. RAS
  4. [2.740.11.0101]
  5. [02.514.12.4007]

Ask authors/readers for more resources

Background: Recent progress in sequencing and 3 D structure determination techniques stimulated development of approaches aimed at more precise annotation of proteins, that is, prediction of exact specificity to a ligand or, more broadly, to a binding partner of any kind. Results: We present a method, SDPclust, for identification of protein functional subfamilies coupled with prediction of specificity-determining positions (SDPs). SDPclust predicts specificity in a phylogeny-independent stochastic manner, which allows for the correct identification of the specificity for proteins that are separated on a phylogenetic tree, but still bind the same ligand. SDPclust is implemented as a Web-server http://bioinf.fbb.msu.ru/SDPfoxWeb/ and a stand-alone Java application available from the website. Conclusions: SDPclust performs a simultaneous identification of specificity determinants and specificity groups in a statistically robust and phylogeny-independent manner.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.0
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Biochemical Research Methods

Phylogenetic inference of changes in amino acid propensities with single-position resolution

Galya Klink, Olga Kalinina, Georgii Bazykin

Summary: Fitness conferred by the same allele may differ between genotypes and environments, and these differences shape variation and evolution. In this study, a new method is developed to detect individual amino acids that confer different fitness in different groups of species. The method combines sequence and phylogenetic data, and is validated using simulated evolution and applied to HIV-1 and influenza A. The results are consistent with fitness differences observed in experiments.

PLOS COMPUTATIONAL BIOLOGY (2022)

Article Biochemistry & Molecular Biology

PRECOGx: exploring GPCR signaling mechanisms with deep protein representations

Marin Matic, Gurdeep Singh, Francesco Carli, Natalia De Oliveira Rosa, Pasquale Miglionico, Lorenzo Magni, J. Silvio Gutkind, Robert B. Russell, Asuka Inoue, Francesco Raimondi

Summary: This study demonstrates that protein language models can encode structural and functional information of GPCR sequences for predicting their signaling and functional repertoire. The researchers developed a machine learning predictor called PRECOGx, which outperforms its predecessor PRECOG in predicting GPCR-transducer couplings and considers all GPCR classes. The study also introduces new functionalities in a webserver, allowing for the projection of input sequences and analysis of sequence and structural determinants responsible for coupling.

NUCLEIC ACIDS RESEARCH (2022)

Article Multidisciplinary Sciences

The S-palmitoylome and DHHC-PAT interactome of Drosophila melanogaster S2R+cells indicate a high degree of conservation to mammalian palmitoylomes

Elena Porcellato, Juan Carlos Gonzalez-Sanchez, Constantin Ahlmann-Eltze, Mahmoud Ali Elsakka, Itamar Shapira, Juergen Fritsch, Juan Antonio Navarro, Simon Anders, Robert B. Russell, Felix T. Wieland, Christoph Metzendorf

Summary: Protein S-palmitoylation, a reversible protein modification, plays a crucial role in neuronal diseases and cancer. However, its study in Drosophila melanogaster has been limited. In this study, the palmitoylome of Drosophila S2R+ cells was analyzed, and a method called DHHC-BioID was established to identify client proteins and interaction partners of protein acyl-transferases (PATs). The results showed that S-palmitoylated proteins are conserved between mammals and Drosophila, and DHHC-BioID is a sensitive and specific method for identifying DHHC-PAT client proteins.

PLOS ONE (2022)

Article Multidisciplinary Sciences

Recapitulation of the embryonic transcriptional program in holometabolous insect pupae

Alexandra M. Ozerova, Mikhail S. Gelfand

Summary: Holometabolous insects show significant changes in gene expression during metamorphosis, resembling the embryonic stage rather than the larval stage. The transition from pupa to imago shows similar gene expression patterns as the transition from embryo to larva. Genes associated with metabolism and development undergo changes in expression levels during the larval stage and revert to an embryonic-like state during metamorphosis.

SCIENTIFIC REPORTS (2022)

Article Genetics & Heredity

Never-homozygous genetic variants in healthy populations are potential recessive disease candidates

Torsten Schmenger, Gaurav D. Diwan, Gurdeep Singh, Gordana Apic, Robert B. Russell

Summary: The rapid pace of genetic variant discovery is crucial for understanding their impact on biological systems. By studying genetic variants in healthy individuals, we identified potential disease-causing variants that have an impact on biological function. These findings suggest the presence of many relatively common lethal or disease-causing variants in healthy human populations.

NPJ GENOMIC MEDICINE (2022)

Article Biochemistry & Molecular Biology

Biochemically validated structural model of the 15-subunit intraflagellar transport complex IFT-B

Narcis A. Petriman, Marta Loureiro-Lopez, Michael Taschner, Nevin K. Zacharia, Magdalena M. Georgieva, Niels Boegholm, Jiaolong Wang, Andre Mourao, Robert B. Russell, Jens S. Andersen, Esben Lorentzen

Summary: Cilia are essential organelles for cellular functions such as motility, signaling, and sensory reception. In this study, the researchers used Alphafold to model the structure of the IFT-B complex, which is involved in cilium formation. The results provide insights into the assembly and function of the IFT-B complex.

EMBO JOURNAL (2022)

Article Multidisciplinary Sciences

The human signal peptidase complex acts as a quality control enzyme for membrane proteins

Andrea Zanotti, Joao P. L. Coelho, Dinah Kaylani, Gurdeep Singh, Marina Tauber, Manuel Hitzenberger, Donem Avci, Martin Zacharias, Robert B. Russell, Marius K. Lemberg, Matthias J. Feige

Summary: This study reveals a previously unknown function of the human signal peptidase complex (SPC) as a membrane protein quality control factor. The SPC cleaves membrane proteins at hidden cleavage sites when they fail to fold or assemble correctly, contributing to membrane protein homeostasis and cellular fitness.

SCIENCE (2022)

Article Cell Biology

A targeted multi-proteomics approach generates a blueprint of the ciliary ubiquitinome

Mariam G. Aslanyan, Cenna Doornbos, Gaurav D. Diwan, Zeinab Anvarian, Tina Beyer, Katrin Junger, Sylvia E. C. van Beersum, Robert B. Russell, Marius Ueffing, Alexander Ludwig, Karsten Boldt, Lotte B. Pedersen, Ronald Roepman

Summary: By studying ubiquitination modifications in cells, we have identified the involvement of ESCRT-dependent clathrin-mediated endocytosis vesicles and caveolae components in ciliary function. These findings contribute to a better understanding of the mechanisms underlying cilia biology in health and disease.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2023)

Article Multidisciplinary Sciences

Data on the temporal changes in soil properties and microbiome composition after a jet-fuel contamination during the pot and field experiments

Ivan N. Semenkov, Pavel Shelyakin, Daria D. Nikolaeva, Maria N. Tutukina, Anna Sharapova, Sergey A. Lednev, Yuliya Sarana, Mikhail S. Gelfand, Pavel P. Krechetov, Tatiana Koroleva

Summary: This article presents original data on the impact of jet-fuel spillage on topsoil properties. The data set includes information on kerosene concentration over time, as well as physicochemical and biological properties of the soil. Additionally, sequencing data on microbial communities are provided.

DATA IN BRIEF (2023)

Article Chemistry, Multidisciplinary

Unusual peptide-binding proteins guide pyrroloindoline alkaloid formation in crocagin biosynthesis

Sebastian Adam, Dazhong Zheng, Andreas Klein, Carsten Volz, William Mullen, Sally L. Shirran, Brian O. Smith, Olga V. Kalinina, Rolf Mueller, Jesko Koehnke

Summary: In this study, we identified three proteins (CgnB, CgnC, and CgnE) responsible for the production of the tetracyclic crocagin core. Crystal structures of two homologues (CgnB and CgnE) provided insights into their functions. We also discovered the roles of CgnD and CgnL in the liberation and modification of the crocagin core, respectively, and proposed a biosynthetic scheme. Bioinformatic analyses further revealed potential pathways for the synthesis of structurally diverse peptide-derived pyrroloindoline alkaloids.

NATURE CHEMISTRY (2023)

Review Biochemistry & Molecular Biology

Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder

Fabiola De Marchi, Toni Franjkic, Paride Schito, Tommaso Russo, Jerneja Nimac, Anna A. Chami, Angelica Mele, Lea Vidatic, Jasna Kriz, Jean-Pierre Julien, Gordana Apic, Robert B. Russell, Boris Rogelj, Jason R. Cannon, Marco Baralle, Federica Agosta, Silva Hecimovic, Letizia Mazzini, Emanuele Buratti, Ivana Munitic

Summary: Proteinopathy and neuroinflammation are two main features of neurodegenerative diseases with high heterogeneity. This review focuses on ALS and FTD spectrum disorder, highlighting neuroinflammation and immune imbalance as novel therapeutic targets. Dysregulation of TDP-43 is a common mechanism in most ALS and 50% of FTD patients, leading to altered cellular events. Experimental attempts targeting TDP-43 aggregates and inflammation will be discussed.

BIOMEDICINES (2023)

Article Biochemical Research Methods

MetaProFi: an ultrafast chunked Bloom filter for storing and querying protein and nucleotide sequence data for accurate identification of functionally relevant genetic variants

Sanjay K. Srikakulam, Sebastian Keller, Fawaz Dabbaghie, Robert Bals, Olga Kalinina

Summary: MetaProFi is a Bloom filter-based tool that allows rapid searches in large sequence datasets. It is the first tool that can build indexes of amino acid sequences and query them with both amino acid and nucleotide sequences, bringing sequence comparison to the biologically relevant protein level.

BIOINFORMATICS (2023)

Article Cell Biology

De-Suppression of Mesenchymal Cell Identities and Variable Phenotypic Outcomes Associated with Knockout of Bbs1

Grace Mercedes Freke, Tiago Martins, Rosalind Jane Davies, Tina Beyer, Marian Seda, Emma Peskett, Naila Haq, Avishek Prasai, Georg Otto, Jeshmi Jeyabalan Srikaran, Victor Hernandez, Gaurav D. Diwan, Robert B. Russell, Marius Ueffing, Martina Huranova, Karsten Boldt, Philip L. Beales, Dagan Jenkins

Summary: Bardet-Biedl syndrome is a ciliopathy that affects multiple tissues. Research suggests that BBS1 plays a crucial role in suppressing the transition from epithelial cells to mesenchymal cells, and dysregulation of epithelial-to-mesenchymal transition genes may be a predisposing feature of BBS.

CELLS (2023)

Article Biology

d-StructMAn: Containerized structural annotation on the scale from genetic variants to whole proteomes

Alexander Gress, Sanjay K. Srikakulam, Sebastian Keller, Vasily Ramensky, Olga Kalinina

Summary: This study presents a novel computational method called d-StructMAn for structural annotation of local genetic variants. By annotating multiple datasets of human genetic variants, it was found that d-StructMAn can provide structural annotation for a significant portion of the human proteome. This method is instrumental in predicting genotype-to-phenotype relationships.

GIGASCIENCE (2022)

No Data Available