Phosphate-binding loop and Rab GTPase function: mutations at Ser29 and Ala30 of Rab5 lead to loss-of-function as well as gain-of-function phenotype

The Biochemical Journal
G Li, Z Liang

Abstract

Ras-like GTPases contain a structurally conserved GTP-binding domain. An important element of the GTP-binding domain is the phosphate-binding loop, which contains two Gly residues (Gly(12) and Gly(13)) in Ras. Because the two Gly residues are crucial for normal Ras function, it is intriguing that they are not conserved in other Ras-like GTPases, including the Rab GTPases; for example, the equivalent residues in Rab5 are Ser(29) and Ala(30). The present study builds on earlier biochemical characterizations of the Rab5 mutants containing substitutions at Ala(30) and provides a comprehensive analysis of the structure-function relationship of the Rab5 phosphate-binding loop. We have generated 19 new mutants containing amino acid substitutions at Ser(29) and determined whether these Ser(29) mutants, as well as the Ala(30) mutants, remain able to stimulate the endocytosis of horseradish peroxidase in baby hamster kidney cells. A total of 11 mutants lose the activity of stimulating endocytosis. Of these 11 mutants, 9 are defective in membrane association. In contrast, 27 mutants remain able to stimulate endocytosis. Five of them induce a novel cellular phenotype: cell rounding and detachment from culture dishes. They also induce super...Continue Reading

Citations

Oct 13, 2009·Biochemical and Biophysical Research Communications·Jing-Fang Wang, Kuo-Chen Chou
Oct 4, 2008·The American Journal of Pathology·Kazuhiro OsanaiDennis R Voelker
Jul 9, 2004·Journal of Molecular Biology·Guangpu Li, Xuejun C Zhang
Jan 5, 2016·Journal of Biomolecular Structure & Dynamics·Faez Iqbal KhanMd Imtaiyaz Hassan
Aug 13, 2015·BMC Structural Biology·Fabio C RinaldiRuth Collins
Feb 4, 2009·FEMS Microbiology Letters·Jiangjiao LiWei Wang
Mar 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Stacie K LoftusWilliam J Pavan
Aug 19, 2007·Molecular Biology of the Cell·Huaiping ZhuGuangpu Li
Feb 3, 2007·Molecular Biology of the Cell·Jay LiuGuangpu Li
Sep 21, 2004·Nature Structural & Molecular Biology·Guangyu ZhuXuejun C Zhang
Oct 29, 2004·Plant & Cell Physiology·Gil-Je LeeInhwan Hwang
Oct 23, 2008·Traffic·Hye-Young YoonPaul A Randazzo
Oct 19, 2005·Plant & Cell Physiology·Jae Bok HeoJeong Dong Bahk
Oct 18, 2006·The Journal of Cell Biology·Christina WasmeierMiguel C Seabra
Jul 14, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Magdalena M GorskaRafeul Alam
Aug 1, 2018·International Journal of Molecular Sciences·Kazuhiro Osanai
Feb 20, 2003·Archives of Biochemistry and Biophysics·Jochen KuperGünter Schwarz
Dec 19, 2003·Biochemical and Biophysical Research Communications·Jane DingWilliam A Maltese

❮ 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.