Detailed molecular dynamics simulations of human transferrin provide insights into iron release dynamics at serum and endosomal pH

Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry
Haleh AbdizadehCanan Atilgan

Abstract

Human serum transferrin (hTf) transports ferric ions in the blood stream and delivers them to cells via receptor-mediated endocytosis. hTf is folded into two homologous lobes; we utilize three of the available crystal structures delineating large conformational changes involved in iron binding/dissociation. We address the problems of whether the release process follows the same trend at serum (~7.4) and endosomal (~5.6) pH, and if there is communication between the lobes. In the absence of the transferrin receptor, we study the dynamics of the full structure as well as the separate lobes in different closed, partially open, and open conformations under neutral and endosomal pH conditions. Results corroborate those experimental observations underscoring the distinguishing effect of pH on the dynamics of hTf. Furthermore, in a total of 2 μs molecular dynamics simulations, residue fluctuations elucidate the cross talk between the lobes correlated by the peptide linker bridging them at serum pH, while their correlations are lost under endosomal conditions. At serum pH, interplay between relative mobility of the lobes is correlated with iron release rates, rendering the initial conformational change an important contributor to the d...Continue Reading

References

Apr 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·A Dautry-VarsatH F Lodish
Apr 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·H HuebersC Finch
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Feb 12, 1998·Journal of Molecular Biology·S A MooreE N Baker
Aug 17, 2000·Bioscience, Biotechnology, and Biochemistry·M Hirose
Jul 27, 2001·The International Journal of Biochemistry & Cell Biology·P AisenM Wessling-Resnick
Dec 26, 2001·Chemical Reviews·H SunP J Sadler
Feb 26, 2004·Cell·Yifan ChengThomas Walz
Mar 2, 2005·Best Practice & Research. Clinical Haematology·Nancy C Andrews
Jun 28, 2005·Nucleic Acids Research·John C GordonAlexey Onufriev
Aug 23, 2005·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Lisa A LambertAnne B Mason
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Oct 24, 2009·PLoS Computational Biology·Canan Atilgan, Ali Rana Atilgan
Jul 7, 2010·Cell·Matthias W HentzeClara Camaschella
Aug 17, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Ashley N SteereAnne B Mason
Nov 26, 2010·Journal of the American Chemical Society·Paolo Raiteri, Julian D Gale
Jun 28, 2011·Biochimica Et Biophysica Acta·Ashley N SteereAnne B Mason
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Brian E EckenrothAnne B Mason
Aug 19, 2011·Biochimica Et Biophysica Acta·Wesley R Harris
Aug 23, 2011·Biochimica Et Biophysica Acta·Alex D SheftelPrem Ponka
Feb 14, 2012·Nature·Nicholas NoinajSusan K Buchanan
May 26, 2012·The Journal of Physical Chemistry. B·Sunita NegiCanan Atilgan

❮ Previous
Next ❯

Citations

Mar 15, 2016·Analytical Chemistry·Ahmad KenaanAnne Magali Charrier
Apr 20, 2017·Physical Chemistry Chemical Physics : PCCP·Haleh AbdizadehCanan Atilgan
Apr 27, 2017·The Journal of Physical Chemistry. B·Haleh AbdizadehCanan Atilgan
Feb 14, 2017·Physical Chemistry Chemical Physics : PCCP·Ozge SensoyCanan Atilgan
Oct 3, 2017·Metallomics : Integrated Biometal Science·H AbdizadehB Dedeoglu
Oct 3, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Nicole AdamPetra J Panak
Nov 17, 2020·Frontiers in Molecular Biosciences·Haleh AbdizadehCanan Atilgan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.