The multiple roles of epidermal growth factor repeatO-glycans in animal development DOI
Amanda R. Haltom, Hamed Jafar‐Nejad

Glycobiology, Journal Year: 2015, Volume and Issue: 25(10), P. 1027 - 1042

Published: July 14, 2015

The epidermal growth factor (EGF)-like repeat is a common, evolutionarily conserved motif found in secreted proteins and the extracellular domain of transmembrane proteins. EGF repeats harbor six cysteine residues which form three disulfide bonds help generate three-dimensional structure repeat. A subset consensus sequences for addition one or more specific O-glycans, are initiated by O-glucose, O-fucose O-N-acetylglucosamine. These glycans relatively rare compared to mucin-type O-glycans. However, genetic experiments model organisms cell-based assays indicate that at least some glycosyltransferases involved O-glycans play important roles animal development. studies, combined with state-of-the-art biochemical structural biology have started provide an in-depth picture how these regulate function they linked. In this review, we will discuss biological assigned corresponding glycosyltransferases. Since Notch receptors best studied biologically-relevant on repeats, significant part review devoted role regulation signaling pathway. We also recently identified other than depend properly. Several elongation mutated human diseases. Therefore, mechanistic understanding functional carbohydrate modifications interest from both basic science translational perspectives.

Language: Английский

Biological roles of glycans DOI Open Access
Ajit Varki

Glycobiology, Journal Year: 2016, Volume and Issue: 27(1), P. 3 - 49

Published: Aug. 24, 2016

Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural physical roles in biological systems. Targeted microbial binding host glycans has also studied for decades. But such can only explain some of the remarkable complexity organismal diversity nature. Reviewing subject about two decades ago, one could find very few clear-cut instances glycan-recognition-specific that were intrinsic value organism expressing them. In striking contrast there is now a profusion examples, this updated review cannot be comprehensive. Instead, historical overview presented, broad principles outlined examples cited, representing diverse types roles, mediated by various glycan classes, different evolutionary lineages. What remains unchanged fact while all theories regarding are supported compelling evidence, exceptions each found. retrospect, not surprising. Complex appear ubiquitous cells nature, essential life forms. Thus, >3 billion years evolution consistently generated organisms use these molecules many key even sometimes coopting them minor functions. respect, no from other macromolecular building blocks (nucleic acids, proteins lipids), simply more rapidly evolving complex. It time functional fully incorporated into mainstream sciences.

Language: Английский

Citations

2207

Glycosylation in health and disease DOI Open Access
Colin Reily,

Tyler J. Stewart,

Matthew B. Renfrow

et al.

Nature Reviews Nephrology, Journal Year: 2019, Volume and Issue: 15(6), P. 346 - 366

Published: March 11, 2019

Language: Английский

Citations

1632

Perspectives on Glycosylation and Its Congenital Disorders DOI Creative Commons
Bobby G. Ng, Hudson H. Freeze

Trends in Genetics, Journal Year: 2018, Volume and Issue: 34(6), P. 466 - 476

Published: March 29, 2018

Language: Английский

Citations

208

Congenital disorders of glycosylation DOI Creative Commons
Irene J. Chang, Miao He, Christina Lam

et al.

Annals of Translational Medicine, Journal Year: 2018, Volume and Issue: 6(24), P. 477 - 477

Published: Dec. 1, 2018

Abstract: Congenital disorders of glycosylation are a genetically and clinically heterogeneous group >130 diseases caused by defects in various steps along glycan modification pathways. The vast majority these monogenic autosomal recessive have multi-systemic manifestations, mainly growth failure, developmental delay, facial dysmorphisms, variable coagulation endocrine abnormalities. Carbohydrate deficient transferrin (CDT) protein-linked analysis with mass spectrometry can diagnose some subtypes congenital (CDG), while many currently rely on massively parallel genomic sequencing for diagnosis. Early detection is important, as few treatable. Molecular biochemical techniques continue to further our understanding this rapidly expanding diverse disorders.

Language: Английский

Citations

194

Glycoproteomics DOI Open Access
Ieva Bagdonaite, Stacy A. Malaker, Daniel A. Polasky

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: June 23, 2022

Language: Английский

Citations

156

Mammalian brain glycoproteins exhibit diminished glycan complexity compared to other tissues DOI Creative Commons
Sarah Williams, Maxence Noël, Sylvain Lehoux

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 12, 2022

Abstract Glycosylation is essential to brain development and function, but prior studies have often been limited a single analytical technique excluded region- sex-specific analyses. Here, using several methodologies, we analyze Asn-linked Ser/Thr/Tyr-linked protein glycosylation between regions sexes in mice. Brain N-glycans are less complex sequence variety compared other tissues, consisting predominantly of high-mannose fucosylated/bisected structures. Most O-glycans unbranched, sialylated O-GalNAc O-mannose A consistent pattern observed regions, sex differences minimal those plasma. glycans correlate with RNA expression their synthetic enzymes, analysis genes humans show global downregulation the tissues. We hypothesize that this restricted repertoire arises from tight regulation brain. These results provide roadmap for future neurodevelopment disease.

Language: Английский

Citations

77

Comprehensive Overview of Bottom-Up Proteomics Using Mass Spectrometry DOI Creative Commons
Yuming Jiang, Rex Devasahayam Arokia Balaya, Dina Schuster

et al.

ACS Measurement Science Au, Journal Year: 2024, Volume and Issue: 4(4), P. 338 - 417

Published: June 4, 2024

Proteomics is the large scale study of protein structure and function from biological systems through identification quantification."Shotgun proteomics" or "bottom-up prevailing strategy, in which proteins are hydrolyzed into peptides that analyzed by mass spectrometry.Proteomics studies can be applied to diverse ranging simple proteoforms, protein-protein interactions, structural alterations, absolute relative quantification, post-translational modifications, stability.To enable this range different experiments, there strategies for proteome analysis.The nuances how proteomic workflows differ may challenging understand new practitioners.Here, we provide a comprehensive overview proteomics methods.We cover biochemistry basics extraction interpretation orthogonal validation.We expect Review will serve as handbook researchers who field bottom-up proteomics.

Language: Английский

Citations

27

What is new in CDG? DOI
Jaak Jaeken, Romain Péanne

Journal of Inherited Metabolic Disease, Journal Year: 2017, Volume and Issue: 40(4), P. 569 - 586

Published: May 8, 2017

Language: Английский

Citations

148

Protein Sequence Editing of SKN-1A/Nrf1 by Peptide:N-Glycanase Controls Proteasome Gene Expression DOI Creative Commons
Nicolas J. Lehrbach,

Peter C. Breen,

Gary Ruvkun

et al.

Cell, Journal Year: 2019, Volume and Issue: 177(3), P. 737 - 750.e15

Published: April 1, 2019

Language: Английский

Citations

111

Integrative glycoproteomics reveals protein N-glycosylation aberrations and glycoproteomic network alterations in Alzheimer’s disease DOI Creative Commons
Qi Zhang, Cheng Ma, Lih‐Shen Chin

et al.

Science Advances, Journal Year: 2020, Volume and Issue: 6(40)

Published: Oct. 2, 2020

Disease-associated glycoproteome changes identified in human brain provide new insights into Alzheimer’s disease pathogenesis.

Language: Английский

Citations

88