The I-TASSER Suite: protein structure and function prediction

Yang, Jianyi; Yan, Renxiang; Roy, Ambrish; Xu, Dong; Poisson, Jonathan; Zhang, Yang

doi:10.1038/nmeth.3213

Cited by 5,167 publications

(4,287 citation statements)

References 6 publications

Supporting

Mentioning

4,126

Contrasting

Unclassified

Order By: Relevance

“…2010; Yang et al . 2014) using available crystal structures of prokaryotic CCC cytoplasmic tail (PDB 3G40; Warmuth et al . 2009) and full‐length prokaryotic amino acid transporters (PDB 3GI9; Shaffer et al .…”

Section: Discussionmentioning

confidence: 99%

Regulation of neuronal chloride homeostasis by neuromodulators

Mahadevan

Woodin

2016

The Journal of Physiology

View full text Add to dashboard Cite

KCC2 is the central regulator of neuronal Cl− homeostasis, and is critical for enabling strong hyperpolarizing synaptic inhibition in the mature brain. KCC2 hypofunction results in decreased inhibition and increased network hyperexcitability that underlies numerous disease states including epilepsy, neuropathic pain and neuropsychiatric disorders. The current holy grail of KCC2 biology is to identify how we can rescue KCC2 hypofunction in order to restore physiological levels of synaptic inhibition and neuronal network activity. It is becoming increasingly clear that diverse cellular signals regulate KCC2 surface expression and function including neurotransmitters and neuromodulators. In the present review we explore the existing evidence that G‐protein‐coupled receptor (GPCR) signalling can regulate KCC2 activity in numerous regions of the nervous system including the hypothalamus, hippocampus and spinal cord. We present key evidence from the literature suggesting that GPCR signalling is a conserved mechanism for regulating chloride homeostasis. This evidence includes: (1) the activation of group 1 metabotropic glutamate receptors and metabotropic Zn2+ receptors strengthens GABAergic inhibition in CA3 pyramidal neurons through a regulation of KCC2; (2) activation of the 5‐hydroxytryptamine type 2A serotonin receptors upregulates KCC2 cell surface expression and function, restores endogenous inhibition in motoneurons, and reduces spasticity in rats; and (3) activation of A3A‐type adenosine receptors rescues KCC2 dysfunction and reverses allodynia in a model of neuropathic pain. We propose that GPCR‐signals are novel endogenous Cl− extrusion enhancers that may regulate KCC2 function.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of neuronal chloride homeostasis by neuromodulators

Mahadevan

Woodin

2016

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…The initial template of rGLP-1R TM domain was derived from a homology-based model calculated by I-TASSER 51 . The crystal structure of GLP-1R NTD:GLP-1 complex (PDB ID: 3IOL) and β2AR:Gs complex (PDB ID: 3SN6) were used as initial models for NTD-hGLP-1 and Gs heterotrimer, respectively.…”

Section: Methodsmentioning

confidence: 99%

Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein

Zhang

Sun

Feng

et al. 2017

Nature

503

568

View full text Add to dashboard Cite

Summary Glucagon-like peptide-1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to GLP-1R, a family B G protein-coupled receptor (GPCR) signaling primarily through the stimulatory G protein Gs. Family B GPCRs are important therapeutic targets, however our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors. Here we show the electron cryo-microscopy structure of the peptide-activated GLP-1R:Gs complex at near atomic resolution. The peptide is clasped between the N-terminal domain and transmembrane core of the receptor, further stabilized by extracellular loops. Conformational changes in the transmembrane domain result in a sharp kink in the middle of transmembrane helix 6, which pivots its intracellular half outward to accommodate the α5 helix of GαsRas. These results provide a structural framework for understanding family B receptor activation through hormone binding.

show abstract

“…Homology-based 3-D structure 3-D modeling was done with I-TASSER (Yang et al 2015b), which starts from experimentally determined structure templates in the PDB library and uses multiple threading programs by LOMETS, each of which can generate thousands of alignments. I-TASSER only accepts templates of the highest significance in the threading alignments measured by Z-score.…”

Section: Sequence Comparisonmentioning

confidence: 99%

On the role, ecology, phylogeny, and structure of dual-family immunophilins

Barik¹

2017

Cell Stress and Chaperones

View full text Add to dashboard Cite

The novel class of dual-family immunophilins (henceforth abbreviated as DFI) represents naturally occurring chimera of classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker that may include a three-unit tetratricopeptide (TPR) repeat. Here, I report a comprehensive analysis of all current DFI sequences and their host organisms. DFIs are of two kinds: CFBP (cyclosporin-and FK506-binding protein) and FCBP (FK506-and cyclosporin-binding protein), found in eukaryotes. The CFBP type occurs in select bacteria that are mostly extremophiles, such as psychrophilic, thermophilic, halophilic, and sulfur-reducing. Essentially all DFI organisms are unicellular. I suggest that DFIs are specialized bifunctional chaperones that use their flexible interdomain linker to associate with large polypeptides or multisubunit megacomplexes to promote simultaneous folding or renaturation of two clients in proximity, essential in stressful and denaturing environments. Analysis of sequence homology and predicted 3D structures of the FKBP and CYN domains as well as the TPR linkers upheld the modular nature of the DFIs and revealed the uniqueness of their TPR domain. The CFBP and FCBP genes appear to have evolved in parallel pathways with no obvious single common ancestor. The occurrence of both types of DFI in multiple unrelated phylogenetic clades supported their selection in metabolic and environmental niche roles rather than a traditional taxonomic relationship.Nonetheless, organisms with these rare immunophilins may define an operational taxonomic unit (OTU) bound by the commonality of chaperone function.

show abstract

The I-TASSER Suite: protein structure and function prediction

Cited by 5,167 publications

References 6 publications

Regulation of neuronal chloride homeostasis by neuromodulators

Regulation of neuronal chloride homeostasis by neuromodulators

Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein

On the role, ecology, phylogeny, and structure of dual-family immunophilins

Contact Info

Product

Resources

About