Structures of ubiquitin insertion mutants support site-specific reflex response to insertions hypothesis

Journal of Molecular Biology
Debra M FerraroAndrew D Robertson

Abstract

We previously concluded that, judging from NMR chemical shifts, the effects of insertions into ubiquitin on its conformation appear to depend primarily on the site of insertion rather than the sequence of the insertion. To obtain a more complete and atomic-resolution understanding of how these insertions modulate the conformation of ubiquitin, we have solved the crystal structures of four insertional mutants of ubiquitin. Insertions between residues 9 and 10 of ubiquitin are minimally perturbing to the remainder of the protein, while larger alterations occur when the insertion is between residues 35 and 36. Further, the alterations in response to insertions are very similar for each mutant at a given site. Two insertions, one at each site, were designed from structurally homologous proteins. Interestingly, the secondary structure within these five to seven amino acid residue insertions is conserved in the new protein. Overall, the crystal structures support the previous conclusion that the conformational effects of these insertions are determined largely by the site of insertion and only secondarily by the sequence of the insert.

References

Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Jul 1, 1990·Acta Crystallographica. Section A, Foundations of Crystallography·A T BrüngerJ W Erickson
Apr 5, 1987·Journal of Molecular Biology·S Vijay-KumarW J Cook
Aug 1, 1995·Current Opinion in Biotechnology·D Shortle, J Sondek
Mar 17, 1995·The Journal of Biological Chemistry·M NukagaT Sawai
Feb 18, 1994·Journal of Molecular Biology·W J CookC M Pickart
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Feb 27, 1999·Current Opinion in Biotechnology·J M Moore
Jul 16, 1999·The EMBO Journal·S C JohnstonC P Hill
Oct 26, 1999·Acta Crystallographica. Section D, Biological Crystallography·J W Pflugrath
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Feb 15, 2001·Acta Crystallographica. Section D, Biological Crystallography·C L PhillipsC P Hill
Apr 11, 2001·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Y KimS J Franklin
Apr 27, 2001·Nature Structural Biology·M J Rudolph, J P Gergen
Jan 10, 2002·Journal of the American Chemical Society·Yugal SharmaNico Tjandra
May 29, 2003·Journal of the American Chemical Society·Roger T KovacicSonya J Franklin
Jun 6, 2003·Cell·Gali PragJames H Hurley
Oct 28, 2003·Proteins·Anna Tramontano, Veronica Morea
May 29, 2004·Pharmacogenomics·Jurgen Kopp, Torsten Schwede
Jan 1, 1993·Acta Crystallographica. Section D, Biological Crystallography·V S Lamzin, K S Wilson
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Apr 5, 2005·Acta Crystallographica. Section D, Biological Crystallography·Airlie J McCoyRandy J Read
Apr 21, 2005·Protein Science : a Publication of the Protein Society·Björn Wallner, Arne Elofsson
Aug 6, 2005·Journal of Molecular Biology·Debra M FerraroAndrew D Robertson
Sep 2, 2005·Nature·UNKNOWN Chimpanzee Sequencing and Analysis Consortium

❮ Previous
Next ❯

Citations

Nov 27, 2007·Journal of Molecular Biology·Debra M Ferraro, Andrew D Robertson
Jun 19, 2007·Journal of Molecular Biology·Thomas A Cutler, Stewart N Loh
Nov 20, 2008·Conservation Biology : the Journal of the Society for Conservation Biology·Steven C Latta, John Faaborg
Feb 14, 2012·Biophysical Journal·Javier OrozMariano Carrión-Vázquez
Nov 3, 2011·Conservation Biology : the Journal of the Society for Conservation Biology·Louise Alexander, George R Hess
Sep 19, 2008·Conservation Biology : the Journal of the Society for Conservation Biology·Finn DanielsenDeki Yonten
Feb 8, 2008·Conservation Biology : the Journal of the Society for Conservation Biology·Jeffrey C MilderBarbara L Bedford
Oct 8, 2014·Acta Crystallographica. Section F, Structural Biology Communications·Patrick J LollScott L Melideo

❮ 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.