Transthyretin (TTR) transports thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3) in the blood of vertebrates. TH-binding sites are highly conserved in vertebrate TTR, however, piscine TTR has a longer N-terminus which is thought to influence TH-binding affinity and may influence TTR stability. We produced recombinant wild type sea bream TTR (sbTTRWT) plus two mutants in which 6 (sbTTRM6) and 12 (sbTTRM12) N-terminal residues were removed. Ligand-binding studies revealed similar affinities for T3 (Kd=10.6+/-1.7nM) and T4 (Kd=9.8+/-0.97nM) binding to sbTTRWT. Affinity for THs was unaltered in sbTTRM12 but sbTTRM6 had poorer affinity for T4 (Kd=252.3+/-15.8nM) implying that some residues in the N-terminus can influence T4 binding. sbTTRM6 inhibited acid-mediated fibril formation in vitro as shown by fluorometric measurements using thioflavine T. In contrast, fibril formation by sbTTRM12 was significant, probably due to decreased stability of the tetramer. Such studies also suggested that sbTTRWT is more resistant to fibril formation than human TTR.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.mce.2008.06.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A study of alpha-synuclein and poly(-isopropylacrylamide) complex formation through detailed atomistic simulations.
Soft Matter
January 2025
Computation-based Science and Technology Research Center, The Cyprus Institute, 2121 Nicosia, Cyprus.
This work presents an investigation of the influence of poly(-isopropylacrylamide) (PNIPAM) polymer on the structural dynamics of intrinsically disordered alpha-synuclein (α-syn) protein, exploring the formation and intricate features of the resulting α-syn/PNIPAM complexes. Using atomistic molecular dynamics (MD) simulations, our study analyzes the impact of initial configuration, polymer molecular weight, and protein mutations on the α-syn and the α-syn/PNIPAM complex. Atomistic simulations, of a few μs, of the protein/polymer complex reveal crucial insights into molecular interactions within the complex, emphasizing a delicate balance of forces governing its stability and structural evolution.
View Article and Find Full Text PDFMisfolding and aggregation of proteins into amyloidogenic assemblies are key features of several metabolic and neurodegenerative diseases. Human insulin has long been known to form amyloid fibrils under various conditions, which affects its bioavailability and function. Clinically, insulin aggregation at recurrent injection sites poses a challenge for diabetic patients who rely on insulin therapy.
View Article and Find Full Text PDFAtrial Cardiomyopathy: From Diagnosis to Treatment.
Rev Cardiovasc Med
January 2025
Department of Cardiology, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China.
With a better understanding of the susceptibility to atrial fibrillation (AF) and the thrombogenicity of the left atrium, the concept of atrial cardiomyopathy (ACM) has emerged. The conventional viewpoint holds that AF-associated hemodynamic disturbances and thrombus formation in the left atrial appendage are the primary causes of cardiogenic embolism events. However, substantial evidence suggests that the relationship between cardiogenic embolism and AF is not so absolute, and that ACM may be an important, underestimated contributor to cardiogenic embolism events.
View Article and Find Full Text PDFMolecular Drivers of Aging in Biomolecular Condensates: Desolvation, Rigidification, and Sticker Lifetimes.
PRX Life
June 2024
Department of Chemistry, Iowa State University, Ames, Iowa 50011, USA.
Biomolecular condensates are dynamic intracellular entities defined by their sequence- and composition-encoded material properties. During aging, these properties can change dramatically, potentially leading to pathological solidlike states, the mechanisms of which remain poorly understood. Recent experiments reveal that the aging of condensates involves a complex interplay of solvent depletion, strengthening of sticker links, and the formation of rigid structural segments such as beta fibrils.
View Article and Find Full Text PDFRecent advances in nutraceutical delivery systems constructed by protein-polysaccharide complexes: A systematic review.
Compr Rev Food Sci Food Saf
January 2025
State Key Laboratory of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao, China.
Most nutraceuticals have low stability and solubility, making it difficult to achieve ideal bioavailability by directly incorporating into food. Therefore, constructing delivery systems to protect nutraceuticals is an essential strategy. Proteins and polysaccharides have become ideal materials for encapsulating nutraceuticals due to their superior nutritional value, edible safety, and physicochemical properties.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!