Protein domains are functionally and structurally independent modules, which add to the functional variety of proteins. This array of functional diversity has been enabled by evolutionary changes, such as amino acid substitutions or insertions or deletions, occurring in these protein domains. Length variations (indels) can introduce changes at structural, functional and interaction levels. LenVarDB (freely available at http://caps.ncbs.res.in/lenvardb/) traces these length variations, starting from structure-based sequence alignments in our Protein Alignments organized as Structural Superfamilies (PASS2) database, across 731 structural classification of proteins (SCOP)-based protein domain superfamilies connected to 2 730 625 sequence homologues. Alignment of sequence homologues corresponding to a structural domain is available, starting from a structure-based sequence alignment of the superfamily. Orientation of the length-variant (indel) regions in protein domains can be visualized by mapping them on the structure and on the alignment. Knowledge about location of length variations within protein domains and their visual representation will be useful in predicting changes within structurally or functionally relevant sites, which may ultimately regulate protein function. Non-technical summary: Evolutionary changes bring about natural changes to proteins that may be found in many organisms. Such changes could be reflected as amino acid substitutions or insertions-deletions (indels) in protein sequences. LenVarDB is a database that provides an early overview of observed length variations that were set among 731 protein families and after examining >2 million sequences. Indels are followed up to observe if they are close to the active site such that they can affect the activity of proteins. Inclusion of such information can aid the design of bioengineering experiments.
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http://dx.doi.org/10.1093/nar/gkt1014 | DOI Listing |
EMBO J
January 2025
Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA.
The complement system and neutrophils constitute the two main pillars of the host innate immune defense against infection by bacterial pathogens. Here, we identify T-Mac, a novel virulence factor of the periodontal pathogen Treponema denticola that allows bacteria to evade both defense systems. We show that T-Mac is expressed as a pre-protein that is cleaved into two functional units.
View Article and Find Full Text PDFNat Cell Biol
January 2025
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Outer mitochondrial membrane (OMM) proteins communicate with the cytosol and other organelles, including the endoplasmic reticulum. This communication is important in thermogenic adipocytes to increase the energy expenditure that controls body temperature and weight. However, the regulatory mechanisms of OMM protein insertion are poorly understood.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Background: Epilepsy has a genetic predisposition, yet causal factors and the dynamics of the immune environment in epilepsy are not fully understood.
Methods: We analyzed peripheral blood samples from epilepsy patients, identifying key genes associated with epilepsy risk through Mendelian randomization, using eQTLGen and genome-wide association studies. The peripheral immune environment's composition in epilepsy was explored using CIBERSORT.
Am J Hum Genet
December 2024
Laboratory of Human Genetics & Therapeutics, Genome Institute of Singapore (GIS), A(∗)STAR, Singapore, Singapore; Laboratory of Human Genetics & Therapeutics, BESE, KAUST, Thuwal, Saudi Arabia; Department of Physiology, Cardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address:
Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.
View Article and Find Full Text PDFStructure
January 2025
Department of Computational Chemistry, Lund University, Chemical Centre, P.O. Box 124, 221 00 Lund, Sweden; European Spallation Source ESS ERIC, P.O. Box 176, 221 00 Lund, Sweden. Electronic address:
Lysozyme is a model system for crystallographers. In this issue of Structure, Ramos et al. report atomic resolution neutron structures of lysozyme, which unambiguously show the protonation states and hydrogen-bonding networks of the active site.
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