A functional loop spanning distant domains of glutaminyl-tRNA synthetase also stabilizes a molten globule state

Biochemistry
Rajesh SahaS Roy

Abstract

Molten globule and other disordered states of proteins are now known to play important roles in many cellular processes. From equilibrium unfolding studies of two paralogous proteins and their variants, glutaminyl-tRNA synthetase (GlnRS) and two of its variants [glutamyl-tRNA synthetase (GluRS) and its isolated domains, and a GluRS-GlnRS chimera], we demonstrate that only GlnRS forms a molten globule-like intermediate at low urea concentrations. We demonstrated that a loop in the GlnRS C-terminal anticodon binding domain that promotes communication with the N-terminal domain and indirectly modulates amino acid binding is also responsible for stabilization of the molten globule state. This loop was inserted into GluRS in the eukaryotic branch after the archaea-eukarya split, right around the time when GlnRS evolved. Because of the structural and functional importance of the loop, it is proposed that the insertion of the loop into a putative ancestral GluRS in eukaryotes produced a catalytically active molten globule state. Because of their enhanced dynamic nature, catalytically active molten globules are likely to possess broad substrate specificity. It is further proposed that the putative broader substrate specificity allowed ...Continue Reading

References

Sep 1, 1992·Protein Science : a Publication of the Protein Society·T KiefhaberA Chaffotte
Jul 8, 1994·Journal of Molecular Biology·I Weygand-DurasevićD Söll
Jul 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·M IbbaD Söll
Nov 5, 1999·Journal of Molecular Biology·P E Wright, H J Dyson
Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
May 31, 2001·Journal of Molecular Graphics & Modelling·A K DunkerZ Obradovic
Sep 5, 2002·Proteins·Mineyuki MizuguchiKatsutoshi Nitta
Jun 26, 2003·Nucleic Acids Research·Takeshi Kawabata
Jul 8, 2003·The Journal of Biological Chemistry·Amit Kumar MandalSiddhartha Roy
Sep 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Stephane SkouloubrisTamara L Hendrickson
Nov 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Juan C SalazarDieter Söll
Mar 23, 2004·Nucleic Acids Research·Robert C Edgar
Jun 3, 2004·Genome Research·Gavin E CrooksSteven E Brenner
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Katherina VamvacaDonald Hilvert
Sep 29, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nathan T Uter, John J Perona
Jun 22, 2005·Biochemistry·Soumi GuhaKankan Bhattacharyya
Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
Jun 1, 2006·Biochemistry·Jiangang LiuA Keith Dunker
Jul 14, 2006·Bioinformatics·Ketil MaldeInge Jonassen
Nov 14, 2007·The Journal of Biological Chemistry·Nunilo CremadesJavier Sancho
Feb 8, 2008·The EMBO Journal·Ann-Bin ShyuAmbro van Hoof
May 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Timothy L BullockJohn J Perona
Sep 10, 2008·Proceedings of the National Academy of Sciences of the United States of America·Maite RocaArieh Warshel
Sep 27, 2008·The Biochemical Journal·Rajesh SahaSiddhartha Roy
Apr 18, 2009·Science·Sebastiaan H MeijsingKeith R Yamamoto
Jun 2, 2009·FEBS Letters·Saumya DasguptaGautam Basu
Sep 9, 2010·Current Opinion in Chemical Biology·Buyong Ma, Ruth Nussinov
Dec 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Patrick O'DonoghueDieter Söll

❮ 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.