Androgen receptor ligand-binding domain interaction and nuclear receptor specificity of FXXLF and LXXLL motifs as determined by L/F swapping

Molecular Endocrinology
Hendrikus J DubbinkJ Trapman

Abstract

The androgen receptor (AR) ligand-binding domain (LBD) binds FXXLF motifs, present in the AR N-terminal domain and AR-specific cofactors, and some LXXLL motifs of nuclear receptor coactivators. We demonstrated that in the context of the AR FXXLF motif many different amino acid residues at positions +2 and +3 are compatible with strong AR LBD interaction, although a preference for E at +2 and K or R at +3 was found. Pairwise systematic analysis of F/L swaps at +1 and +5 in FXXLF and LXXLL motifs showed: 1) F to L substitutions in natural FXXLF motifs abolished AR LBD interaction; 2) binding of interacting LXXLL motifs was unchanged or increased upon L to F substitutions; 3) certain noninteracting LXXLL motifs became strongly AR-interacting FXXLF motifs; whereas 4) other nonbinders remained unaffected by L to F substitutions. All FXXLF motifs, but not the corresponding LXXLL motifs, displayed a strong preference for AR LBD. Progesterone receptor LBD interacted with some FXXLF motifs, albeit always less efficiently than corresponding LXXLL motifs. AR LBD interaction of most FXXLF and LXXLL peptides depended on classical charge clamp residue K720, whereas E897 was less important. Other charged residues lining the AR coactivator-bin...Continue Reading

References

Mar 25, 1992·Nucleic Acids Research·D GietzR H Schiestl
Jun 1, 1995·Endocrine Reviews·C A QuigleyF S French
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·G JensterB W O'Malley
Jun 26, 1998·Current Opinion in Cell Biology·D Moras, H Gronemeyer
Nov 10, 1998·Genes & Development·B D DarimontK R Yamamoto
Jul 27, 1999·The Journal of Steroid Biochemistry and Molecular Biology·A O BrinkmannJ Trapman
Jan 10, 2002·The Journal of Biological Chemistry·Bin HeElizabeth M Wilson
Mar 20, 2002·Nature Reviews. Cancer·B J Feldman, D Feldman
Mar 30, 2002·Molecular Endocrinology·Ching-Yi Chang, Donald P McDonnell
Apr 12, 2002·Endocrine Reviews·Cynthia A Heinlein, Chawnshang Chang
Jun 29, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Edward P Gelmann
Jul 13, 2002·International Journal of Cancer. Journal International Du Cancer·Karine SteketeeJan Trapman
Oct 3, 2002·Nature Reviews. Cancer·James E Darnell
Jan 31, 2003·The Journal of Biological Chemistry·Victoria H CoulthardDavid M Heery
Aug 2, 2003·Molecular Endocrinology·Anette WärnmarkJan-Ake Gustafsson
Dec 20, 2003·Current Topics in Medicinal Chemistry·Holger Greschik, Dino Moras
Jan 6, 2004·Science·Lyubomir T VassilevEmily A Liu
Jun 5, 2004·Molecular Endocrinology·Hendrikus J DubbinkJan Trapman
Jul 28, 2004·Trends in Biochemical Sciences·Laszlo Nagy, John W R Schwabe
Aug 26, 2004·PLoS Biology·Eugene HurRobert J Fletterick
Sep 17, 2004·Endocrine-related Cancer·Howard I ScherWayne D Tilley
Nov 26, 2004·The Journal of Biological Chemistry·Eva Estébanez-PerpiñáR Kiplin Guy
May 20, 2005·Nature·Tilman OltersdorfSaul H Rosenberg
Jul 30, 2005·Molecular Endocrinology·Ching-Yi ChangDonald P McDonnell

❮ Previous
Next ❯

Citations

Dec 17, 2009·The Journal of Biological Chemistry·Dennis J van de WijngaartHendrikus J Dubbink
Oct 23, 2009·The Journal of Biological Chemistry·Geun Bae RhaYoung-In Chi
Jan 21, 2010·The Journal of Biological Chemistry·X Edward ZhouH Eric Xu
May 9, 2012·Cellular and Molecular Life Sciences : CMLS·Alexandra Kollara, Theodore J Brown
May 25, 2011·Molecular and Cellular Endocrinology·Mikhail N ZakharovRavi Jasuja
Sep 19, 2007·Best Practice & Research. Clinical Endocrinology & Metabolism·Jan Trapman, Hendrikus Jan Dubbink
Jan 25, 2013·Medicinal Research Reviews·Laura Caboni, David G Lloyd
Aug 30, 2011·Molecular and Cellular Endocrinology·Jarmo Jääskeläinen
Aug 30, 2011·Molecular and Cellular Endocrinology·Dennis J van de WijngaartGuido Jenster
Oct 22, 2016·ACS Chemical Biology·Yuchen ZhangJohn T Koh
Apr 28, 2020·The Journal of International Medical Research·Seong-Hoon Yun, Joo-In Park
Mar 10, 2015·Oncotarget·Matti AnnalaMatti Nykter
Sep 11, 2019·Assay and Drug Development Technologies·Ashley T FancherPaul A Johnston
Jun 5, 2019·Molecular and Cellular Endocrinology·Kornelia J SkowronTerry W Moore

❮ 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.