scholarly journals Cryo-EM structure of native human thyroglobulin

2021 ◽  
Author(s):  
Ricardo Adaixo ◽  
Eva Steiner ◽  
Ricardo Righetto ◽  
Alexander Schmidt ◽  
Henning Stahlberg ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
3D Structure ◽  
Vital Role ◽  
Hormone Synthesis ◽  
Cryo Electron Microscopy ◽  
Glycosylation Sites ◽  
Regulation Of Metabolism ◽  
Fundamental Understanding ◽  
Insight Into

Abstract The thyroglobulin (Tg) protein is essential to thyroid hormone synthesis, playing a vital role in the regulation of metabolism, development and growth. Its structure is conserved among vertebrates. Tg is delivered through the secretory pathway of the thyroid follicular unit to the central colloid depository, where it is iodinated at specific tyrosine sites to form mono- or diiodotyrosine, which combine to produce triiodothyronine (T3) and thyroxine (T4), respectively. Synthesis of these hormones depends on the precise 3D structure of Tg, which has remained unknown despite decades of research. Here, we present the cryo-electron microscopy structure of human thyroglobulin (hTg) to a global resolution of 3.2 Å. The structure provides detailed information on the location of the hTg hormonogenic sites and reveals the position as well as the role of many of its glycosylation sites. Our results offer structural insight into thyroid hormonogenesis and provide a fundamental understanding of clinically relevant hTg mutations, which can improve treatment of thyroid diseases.

scholarly journals Cryo-EM structure of native human thyroglobulin

2021 ◽  
Author(s):  
Ricardo Adaixo ◽  
Eva M. Steiner ◽  
Ricardo D. Righetto ◽  
Alexander Schmidt ◽  
Henning Stahlberg ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
3D Structure ◽  
Vital Role ◽  
Hormone Synthesis ◽  
Cryo Electron Microscopy ◽  
Glycosylation Sites ◽  
Regulation Of Metabolism ◽  
Fundamental Understanding ◽  
Insight Into

The thyroglobulin (Tg) protein is essential to thyroid hormone synthesis, playing a vital role in the regulation of metabolism, development and growth. Its structure is conserved among vertebrates. Tg is delivered through the secretory pathway of the thyroid follicular unit to the central colloid depository, where it is iodinated at specific tyrosine sites to form mono- or diiodotyrosine, which combine to produce triiodothyronine (T3) and thyroxine (T4), respectively. Synthesis of these hormones depends on the precise 3D structure of Tg, which has remained unknown despite decades of research. Here, we present the cryo-electron microscopy structure of human thyroglobulin (hTg) to a global resolution of 3.2 Å. The structure provides detailed information on the location of the hTg hormonogenic sites and reveals the position as well as the role of many of its glycosylation sites. Our results offer structural insight into thyroid hormonogenesis and provide a fundamental understanding of clinically relevant hTg mutations, which can improve treatment of thyroid diseases.

scholarly journals Cryo-EM structure of native human thyroglobulin

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Ricardo Adaixo ◽  
Eva M. Steiner ◽  
Ricardo D. Righetto ◽  
Alexander Schmidt ◽  
Henning Stahlberg ◽  
...  
Keyword(s):  
Structural Information ◽  
Vital Role ◽  
Cleavage Sites ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Hormone Synthesis ◽  
Cryo Electron Microscopy ◽  
Glycosylation Sites ◽  
Regulation Of Metabolism ◽  
Thyroid Glands

AbstractThe thyroglobulin (TG) protein is essential to thyroid hormone synthesis, plays a vital role in the regulation of metabolism, development and growth and serves as intraglandular iodine storage. Its architecture is conserved among vertebrates. Synthesis of triiodothyronine (T3) and thyroxine (T4) hormones depends on the conformation, iodination and post-translational modification of TG. Although structural information is available on recombinant and deglycosylated endogenous human thyroglobulin (hTG) from patients with goiters, the structure of native, fully glycosylated hTG remained unknown. Here, we present the cryo-electron microscopy structure of native and fully glycosylated hTG from healthy thyroid glands to 3.2 Å resolution. The structure provides detailed information on hormonogenic and glycosylation sites. We employ liquid chromatography–mass spectrometry (LC-MS) to validate these findings as well as other post-translational modifications and proteolytic cleavage sites. Our results offer insights into thyroid hormonogenesis of native hTG and provide a fundamental understanding of clinically relevant mutations.

Role of Interventional Radiology in Children with Biliary and Gallbladder Diseases

2021 ◽  
Vol 38 (03) ◽  
pp. 356-363
Author(s):  
Anel Yakupovich ◽  
Shankar Rajeswaran ◽  
Jared Green ◽  
James S. Donaldson
Keyword(s):  
Interventional Radiology ◽  
Treatment Approach ◽  
Multidisciplinary Treatment ◽  
Anatomical Variations ◽  
Vital Role ◽  
High Morbidity ◽  
Comprehensive Overview ◽  
Gallbladder Diseases ◽  
Fundamental Understanding

AbstractBiliary and gallbladder diseases in infants and children often present unique diagnostic and therapeutic challenges that require a fundamental understanding of notable biliary diseases and anatomical variations. Surgical and endoscopic approaches that are often the gold standard in adult biliary treatment may be technically challenging and are associated with a high morbidity that may warrant a multidisciplinary treatment approach. This article will provide a comprehensive overview of the biliary conditions where interventional radiology can play a vital role in the diagnosis, management, and treatment. Differences in approach or technique between children and adults will be highlighted.

scholarly journals Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs

2018 ◽  
Author(s):  
David M. Kern ◽  
SeCheol Oh ◽  
Richard K. Hite ◽  
Stephen G. Brohawn
Keyword(s):  
Lipid Bilayers ◽  
Critical Role ◽  
Anion Channel ◽  
Lipid Binding ◽  
Channel Structure ◽  
Anion Channels ◽  
Cryo Electron Microscopy ◽  
Lipid Nanodiscs ◽  
Insight Into

AbstractHypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here we present single-particle cryo-electron microscopy structures of LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction. Constricted and expanded structures reveal coupled dilation of cytoplasmic LRRs and the channel pore, suggesting a mechanism for channel gating by internal stimuli. Conformational and symmetry differences between LRRC8A structures determined in detergent micelles and lipid bilayers related to reorganization of intersubunit lipid binding sites demonstrate a critical role for the membrane in determining channel structure. These results provide insight into LRRC8 gating and inhibition and the role of lipids in the structure of an ionic-strength sensing ion channel.

Cryo-EM structure of 90S small ribosomal subunit precursors in transition states

Science ◽  
2020 ◽  
Vol 369 (6510) ◽  
pp. 1477-1481 ◽  
Author(s):  
Yifei Du ◽  
Weidong An ◽  
Xing Zhu ◽  
Qi Sun ◽  
Jia Qi ◽  
...  
Keyword(s):  
Structural Changes ◽  
Critical Role ◽  
Ribosomal Subunit ◽  
Rna Degradation ◽  
Ribosomal Subunits ◽  
Cryo Electron Microscopy ◽  
Nuclear Exosome ◽  
Assembly Intermediate ◽  
Insight Into

The 90S preribosome is a large, early assembly intermediate of small ribosomal subunits that undergoes structural changes to give a pre-40S ribosome. Here, we gained insight into this transition by determining cryo–electron microscopy structures of Saccharomyces cerevisiae intermediates in the path from the 90S to the pre-40S. The full transition is blocked by deletion of RNA helicase Dhr1. A series of structural snapshots revealed that the excised 5′ external transcribed spacer (5′ ETS) is degraded within 90S, driving stepwise disassembly of assembly factors and ribosome maturation. The nuclear exosome, an RNA degradation machine, docks on the 90S through helicase Mtr4 and is primed to digest the 3′ end of the 5′ ETS. The structures resolved between 3.2- and 8.6-angstrom resolution reveal key intermediates and the critical role of 5′ ETS degradation in 90S progression.

scholarly journals Supply chain logistics – the role of the Golgi complex in extracellular matrix production and maintenance

2022 ◽  
Vol 135 (1) ◽  
Author(s):  
John Hellicar ◽  
Nicola L. Stevenson ◽  
David J. Stephens ◽  
Martin Lowe
Keyword(s):  
Extracellular Matrix ◽  
Golgi Complex ◽  
Secretory Pathway ◽  
Biochemical Properties ◽  
Vital Role ◽  
Proteolytic Processing ◽  
Post Translational Modification ◽  
Matrix Components ◽  
The Impact

ABSTRACT The biomechanical and biochemical properties of connective tissues are determined by the composition and quality of their extracellular matrix. This, in turn, is highly dependent on the function and organisation of the secretory pathway. The Golgi complex plays a vital role in directing matrix output by co-ordinating the post-translational modification and proteolytic processing of matrix components prior to their secretion. These modifications have broad impacts on the secretion and subsequent assembly of matrix components, as well as their function in the extracellular environment. In this Review, we highlight the role of the Golgi in the formation of an adaptable, healthy matrix, with a focus on proteoglycan and procollagen secretion as example cargoes. We then discuss the impact of Golgi dysfunction on connective tissue in the context of human disease and ageing.

Assertion, Negotiation and Subjugation of Identity: Understanding the Tamil-Malayali Conflict in Munnar

2019 ◽  
Vol 10 (2) ◽  
pp. 167-182
Author(s):  
Shyam Hari P.
Keyword(s):  
Social Interaction ◽  
Social Identity ◽  
Critical Role ◽  
Vital Role ◽  
Social Identities ◽  
Dynamic Nature ◽  
Major Objective ◽  
Heterogeneous Societies ◽  
Insight Into

Social identities play a critical role in the various phases of conflict. Existing literature often examines the role of social identity of groups in inducing conflict in heterogeneous societies. This article puts forward the view that the role of identity is not limited in terms of inducing conflict, but it also plays a vital role in influencing the dynamics of conflict. Based on this conceptual framework, the article outlines the conflict dynamics observable in the Kannan Devan Hills village in Kerala, where several factors, over the course of time in the last century, have led to the perception of conflict between the Tamils and the Malayalis. As a major objective, the article identifies the issues and processes of social interaction between the two groups that necessarily influence the nature of the conflict. The article identifies that the conflict between the two communities, though mostly latent, can be seen through three important aspects: assertion, negotiation and subjugation of identities. Through assertion of identity, the conflict is perceived over ethnic lines, whereas the process of negotiation and subjugation of identity constantly undermines the ethnic nature of conflict to specific grievances, thus giving insight into the dynamic nature of the conflict.

scholarly journals Long Non-coding RNA: Insight Into Mechanisms of Alzheimer's Disease

2022 ◽  
Vol 14 ◽  
Author(s):  
Zhen Lan ◽  
Yanting Chen ◽  
Jiali Jin ◽  
Yun Xu ◽  
Xiaolei Zhu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Vital Role ◽  
Biological Functions ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna ◽  
Insight Into

Alzheimer's disease (AD), a heterogeneous neurodegenerative disorder, is the most common cause of dementia accounting for an estimated 60–80% of cases. The pathogenesis of AD remains unclear, and no curative treatment is available so far. Increasing evidence has revealed a vital role of non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), in AD. LncRNAs contribute to the pathogenesis of AD via modulating amyloid production, Tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, synaptic impairment and neuroinflammation. This review describes the biological functions and mechanisms of lncRNAs in AD, indicating that lncRNAs may provide potential therapeutic targets for the diagnosis and treatment of AD.

scholarly journals An Integrated Health-System Specialty Pharmacy Model for Coordinating Transitions of Care: Specialty Medication Challenges and Specialty Pharmacist Opportunities

Pharmacy ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 163
Author(s):  
Autumn D. Zuckerman ◽  
Alicia Carver ◽  
Katrina Cooper ◽  
Brandon Markley ◽  
Amy Mitchell ◽  
...  
Keyword(s):  
Best Practices ◽  
Health System ◽  
Vital Role ◽  
Transitions Of Care ◽  
Case Examples ◽  
Specialty Pharmacy ◽  
Specialty Medication ◽  
Insight Into ◽  
Shed Light

Adherence and persistence to specialty medications are necessary to achieve successful outcomes of costly therapies. The increasing use of specialty medications has exposed several unique barriers to certain specialty treatments’ continuation. Integrated specialty pharmacy teams facilitate transitions in sites of care, between different provider types, among prescribed specialty medications, and during financial coverage changes. We review obstacles encountered within these types of transitions and the role of the specialty pharmacist in overcoming these obstacles. Case examples for each type of specialty transition provide insight into the unique complexities faced by patients, and shed light on pharmacists’ vital role in patient care. This insightful and real-world experience is needed to facilitate best practices in specialty care, particularly in the growing number of health-system specialty pharmacies.

Sign in / Sign up

Export Citation Format

Share Document