An extended hydrophobic core induces EF-hand swapping

Protein Science : a Publication of the Protein Society
M HåkanssonS Linse

Abstract

The structure of calbindin D(9k) with two substitutions was determined by X-ray crystallography at 1.8-A resolution. Unlike wild-type calbindin D(9k), which is a monomeric protein with two EF-hands, the structure of the mutated calbindin D(9k) reveals an intertwined dimer. In the dimer, two EF-hands of the monomers have exchanged places, and thus a 3D domain-swapped dimer has been formed. EF-hand I of molecule A is packed toward EF-hand II of molecule B and vice versa. The formation of a hydrophobic cluster, in a region linking the EF-hands, promotes the conversion of monomers to 3D domain-swapped dimers. We propose a mechanism by which domain swapping takes place via the apo form of calbindin D(9k). Once formed, the calbindin D(9k) dimers are remarkably stable, as with even larger misfolded aggregates like amyloids. Thus calbindin D(9k) dimers cannot be converted to monomers by dilution. However, heating can be used for conversion, indicating high energy barriers separating monomers from dimers.

References

Dec 1, 1977·Archives of Biochemistry and Biophysics·P Manavalan, P K Ponnuswamy
Feb 5, 1992·Journal of Molecular Biology·L A SvenssonS Forsén
Nov 15, 1991·Archives of Biochemistry and Biophysics·H M Holden, I Rayment
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Jan 26, 1990·European Journal of Biochemistry·C JohanssonT Drakenberg
Jun 2, 1995·Journal of Molecular Biology·N J SkeltonW J Chazin
Jun 1, 1993·Protein Science : a Publication of the Protein Society·S LinseP Sellers
Mar 15, 1997·Structure·M BergdollP Dumas
Jun 1, 1997·Protein Science : a Publication of the Protein Society·M AnderssonL A Svensson
Jan 1, 1997·Advances in Protein Chemistry·M P SchluneggerD Eisenberg
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Mar 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G J Kleywegt, T A Jones
Jan 1, 1997·Methods in Enzymology·V S Lamzin, K S Wilson

❮ Previous
Next ❯

Citations

Sep 1, 2007·Molecular Biology of the Cell·Regina B TroyanovskySergey M Troyanovsky
Jun 25, 2004·Nucleic Acids Research·Shandar Ahmad, Akinori Sarai
May 22, 2002·Protein Science : a Publication of the Protein Society·Yanshun Liu, David Eisenberg
Aug 23, 2002·Protein Science : a Publication of the Protein Society·Samuel TranierJean-Pierre Samama
Jun 19, 2002·Protein Science : a Publication of the Protein Society·Apichart LinhanantaYaoqi Zhou
Dec 21, 2002·Protein Science : a Publication of the Protein Society·Małgorzata PalczewskaJacek Kuźnicki
Mar 30, 2011·PloS One·Eva ThulinSara Linse
Jun 7, 2005·Proceedings of the National Academy of Sciences of the United States of America·Chien Peter ChenBarry H Honig
Dec 15, 2004·Biophysical Journal·Daniele Dell'OrcoSara Linse
Jul 16, 2017·Protein Science : a Publication of the Protein Society·Neha NandwaniShachi Gosavi
Oct 27, 2007·Protein Science : a Publication of the Protein Society·Jannette CareySara Linse
May 28, 2009·Protein Science : a Publication of the Protein Society·Stina LindmanSara Linse
Mar 3, 2020·Cell Calcium·Sergei E PermyakovEugene A Permyakov
Mar 15, 2006·Journal of Molecular Biology·Cynthia F ShumanSara Linse

❮ 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.