Elucidation of a Copper Binding Site in Proinsulin C-peptide and Its Implications for Metal-Modulated Activity.

Inorganic Chemistry
Michael J StevensonMarie C Heffern

Abstract

The connecting peptide (C-peptide) is a hormone with promising health benefits in ameliorating diabetes-related complications, yet mechanisms remain elusive. Emerging studies point to a possible dependence of peptide activity on bioavailable metals, particularly Cu(II) and Zn(II). However, little is known about the chemical nature of the interactions, hindering advances in its therapeutic applications. This work uncovers the Cu(II)-binding site in C-peptide that may be key to understanding its metal-dependent function. A combination of spectroscopic studies reveal that Cu(II) and Zn(II) bind to C-peptide at specific residues in the N-terminal region of the peptide and that Cu(II) is able to displace Zn(II) for C-peptide binding. The data point to a Cu(II)-binding site consisting of 1N3O square-planar coordination that is entropically driven. Furthermore, the entire random coil peptide sequence is needed for specific metal binding as mutations and truncations reshuffle the coordinating residues. These results expand our understanding of how metals influence hormone activity and facilitate the discovery and validation of both new and established paradigms in peptide biology.

References

Jan 1, 1978·Diabetes·D F Steiner
Jan 1, 1987·Annals of the New York Academy of Sciences·J D CastleG Rudnick
Jan 25, 2002·Nature·Michael Zasloff
Jul 24, 2002·Biochemical and Biophysical Research Communications·Jan JohanssonHans Jörnvall
May 6, 2004·American Journal of Physiology. Endocrinology and Metabolism·Martin J StevensAnders A F Sima
Jun 17, 2004·Experimental Diabesity Research·T Forst, T Kunt
Jul 9, 2005·Cellular and Molecular Life Sciences : CMLS·M HenrikssonH Jörnvall
Jun 6, 2006·Journal of Molecular Graphics & Modelling·Thiago Rennó Mares-GuiaMarcelo Matos Santoro
Aug 19, 2007·Biochimica Et Biophysica Acta·Andreas Barth
Jan 10, 2008·Biochemical and Biophysical Research Communications·Masayuki Nara, Masaru Tanokura
Feb 22, 2008·Journal of Neurochemistry·Vello TõuguPeep Palumaa
Aug 21, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Nicholas E GrossoehmeDean E Wilcox
May 1, 2013·Nature Reviews. Endocrinology·Fred Nyberg, Mathias Hallberg
Sep 23, 2014·Cardiovascular Research·Mahendra Prasad BhattKwon-Soo Ha
Apr 1, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Yueli LiuDana M Spence
Jan 18, 2017·Advances in Nutrition·Veena Sangkhae, Elizabeta Nemeth
Dec 13, 2017·European Journal of Medicinal Chemistry·Małgorzata Jeżowska-Bojczuk, Kamila Stokowa-Sołtys
Mar 30, 2018·Chemical Society Reviews·O ZozuliaI V Korendovych
Oct 3, 2018·Metallomics : Integrated Biometal Science·Michael J StevensonMarie C Heffern
May 11, 2019·Chembiochem : a European Journal of Chemical Biology·Michael J StevensonMarie C Heffern

❮ 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.

Related Papers

Chembiochem : a European Journal of Chemical Biology
Michael J StevensonMarie C Heffern
Horumon to rinsho. Clinical endocrinology
T Kaneko
Horumon to rinsho. Clinical endocrinology
T Kaneko
Annales de médecine interne
M Dorner
© 2022 Meta ULC. All rights reserved