De novo design of the hydrophobic core of ubiquitin

Protein Science : a Publication of the Protein Society
G A LazarT M Handel

Abstract

We have previously reported the development and evaluation of a computational program to assist in the design of hydrophobic cores of proteins. In an effort to investigate the role of core packing in protein structure, we have used this program, referred to as Repacking of Cores (ROC), to design several variants of the protein ubiquitin. Nine ubiquitin variants containing from three to eight hydrophobic core mutations were constructed, purified, and characterized in terms of their stability and their ability to adopt a uniquely folded native-like conformation. In general, designed ubiquitin variants are more stable than control variants in which the hydrophobic core was chosen randomly. However, in contrast to previous results with 434 cro, all designs are destabilized relative to the wild-type (WT) protein. This raises the possibility that beta-sheet structures have more stringent packing requirements than alpha-helical proteins. A more striking observation is that all variants, including random controls, adopt fairly well-defined conformations, regardless of their stability. This result supports conclusions from the cro studies that non-core residues contribute significantly to the conformational uniqueness of these proteins ...Continue Reading

References

Jan 1, 1977·Annual Review of Biophysics and Bioengineering·F M Richards
Jan 1, 1978·Annual Review of Biochemistry·P Y Chou, G D Fasman
Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M S Briggs, H Roder
Apr 14, 1992·Biochemistry·D M SchneiderA J Wand
Nov 1, 1992·Biochemical Society Transactions·J H VeerkampC F Prinsen
Jun 1, 1991·Journal of Biomolecular Structure & Dynamics·P TufferyR Lavery
Jan 20, 1991·Journal of Molecular Biology·C Lee, S Subbiah
Jan 1, 1990·Methods in Enzymology·F W StudierJ W Dubendorff
Aug 7, 1990·Biochemistry·K A Dill
Nov 1, 1989·Analytical Biochemistry·S C Gill, P H von Hippel
Apr 5, 1987·Journal of Molecular Biology·S Vijay-KumarW J Cook
Apr 15, 1982·Archives of Biochemistry and Biophysics·P M Mulqueen, M J Kronman
Nov 1, 1994·Protein Science : a Publication of the Protein Society·M MunsonL Regan
Sep 1, 1994·Protein Science : a Publication of the Protein Society·J M Dabora, S Marqusee
Jul 1, 1994·Protein Science : a Publication of the Protein Society·Y Yan, B W Erickson
May 1, 1994·Biophysical Chemistry·T TanakaH Nakamura
Jun 21, 1994·Proceedings of the National Academy of Sciences of the United States of America·H W Hellinga, F M Richards
Nov 1, 1993·Quarterly Reviews of Biophysics·F M Richards, W A Lim
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·M H Hecht
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·T P QuinnD C Richardson
Mar 1, 1994·Proteins·P L WintrodeP L Privalov
Jan 4, 1994·Proceedings of the National Academy of Sciences of the United States of America·W A LimF M Richards
Jul 13, 1993·Biochemistry·S KhorasanizadehH Roder
Oct 1, 1995·Protein Science : a Publication of the Protein Society·J R Desjarlais, T M Handel
Sep 1, 1995·Journal of Biomolecular NMR·D S WishartB D Sykes
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·D D AxeA R Fersht

❮ Previous
Next ❯

Citations

Dec 24, 2002·Journal of Computational Chemistry·D Benjamin GordonNiles A Pierce
Oct 7, 1998·Protein Science : a Publication of the Protein Society·A J ConstansJ T Lecomte
Nov 25, 1998·Protein Science : a Publication of the Protein Society·E G HutchinsonD N Woolfson
Sep 29, 2011·Journal of Biomolecular NMR·Tairan YuwenNikolai R Skrynnikov
Sep 6, 2011·Journal of Biomolecular NMR·Fabian PetersChristian Griesinger
Jul 26, 2012·Journal of Biomolecular NMR·Joshua M Ward, Nikolai R Skrynnikov
Aug 9, 2013·Journal of Biomolecular NMR·Veniamin ChevelkovAdam Lange
May 28, 2003·Journal of Molecular Biology·Daniel N BolonStephen L Mayo
Aug 28, 1998·Current Opinion in Biotechnology·C E Schafmeister, R M Stroud
Aug 17, 1999·Current Opinion in Biotechnology·B I Dahiyat
Aug 10, 2001·Current Opinion in Structural Biology·D N Woolfson
Aug 7, 2002·Current Opinion in Structural Biology·Joaquim MendesLuis Serrano
Mar 31, 1998·Current Opinion in Structural Biology·V S PandeD S Rokhsar
Sep 8, 1998·Current Opinion in Structural Biology·J R Desjarlais, N D Clarke
Aug 17, 1999·Current Opinion in Structural Biology·D B GordonS L Mayo
Dec 12, 2001·Current Opinion in Chemical Biology·C M Kraemer-PecoreJ R Desjarlais
Jul 17, 1998·Current Opinion in Chemical Biology·B R GibneyP L Dutton
Jan 23, 1999·Current Opinion in Chemical Biology·G A Lazar, T M Handel
Sep 22, 2001·Biomolecular Engineering·I AngrandE Lacroix
Mar 15, 2011·Biochemistry·Hariprasad VenugopalSteven M Pascal
Sep 15, 2011·Journal of the American Chemical Society·Patricio O CraigPeter G Wolynes
Jun 1, 2002·Journal of Biological Physics·J Ervin, M Gruebele
Aug 12, 1998·Nature Structural Biology·S H Kim
Dec 3, 2010·Nature Chemistry·Vikas Nanda, Ronald L Koder
May 20, 1998·Nature Structural Biology·R GilmanshinR B Dyer
Aug 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Oscar Alvizo, Stephen L Mayo
Oct 1, 2009·Nucleic Acids Research·Takeshi SumidaHiroshi Yanagawa
Mar 27, 2001·Protein Science : a Publication of the Protein Society·Z Xu, R S Farid
Mar 29, 2001·Protein Science : a Publication of the Protein Society·S FisingerE Lacroix
Jun 23, 2001·Protein Science : a Publication of the Protein Society·V V LoladzeG I Makhatadze
Jan 13, 2000·Protein Science : a Publication of the Protein Society·G A LazarT M Handel
Jul 1, 1999·Protein Science : a Publication of the Protein Society·K A Dill
Sep 24, 1999·Protein Science : a Publication of the Protein Society·B R Gibney, P L Dutton
Jul 13, 2000·Protein Science : a Publication of the Protein Society·K RahaJ R Desjarlais
Apr 21, 2004·European Journal of Biochemistry·Yawen Bai, Hanqiao Feng
Apr 21, 2004·European Journal of Biochemistry·Thomas J Magliery, Lynne Regan
Jun 29, 2000·Annual Review of Biochemistry·W F DeGradoA Lombardi
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·S T WalshW F DeGrado
Mar 4, 2014·Journal of Biomolecular NMR·Chaowei ShiAdam Lange
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·J SabelkoM Gruebele
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·H W Hellinga
Nov 5, 1999·Journal of Molecular Biology·P Koehl, M Levitt
Sep 25, 2015·International Journal of Molecular Sciences·H Edward Wong, Inchan Kwon

❮ 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

Protein Science : a Publication of the Protein Society
J R Desjarlais, T M Handel
Proceedings of the National Academy of Sciences of the United States of America
B I Dahiyat, S L Mayo
Protein Science : a Publication of the Protein Society
A Su, S L Mayo
Protein Science : a Publication of the Protein Society
B I Dahiyat, S L Mayo
Protein Science : a Publication of the Protein Society
B I DahiyatS L Mayo
© 2021 Meta ULC. All rights reserved