Unusual binding interactions in PDZ domain crystal structures help explain binding mechanisms.

Protein Science : a Publication of the Protein Society
Jonathan M ElkinsD A Doyle

Abstract

PDZ domains most commonly bind the C-terminus of their protein targets. Typically the C-terminal four residues of the protein target are considered as the binding motif, particularly the C-terminal residue (P0) and third-last residue (P-2) that form the major contacts with the PDZ domain's "binding groove". We solved crystal structures of seven human PDZ domains, including five of the seven PDLIM family members. The structures of GRASP, PDLIM2, PDLIM5, and PDLIM7 show a binding mode with only the C-terminal P0 residue bound in the binding groove. Importantly, in some cases, the P-2 residue formed interactions outside of the binding groove, providing insight into the influence of residues remote from the binding groove on selectivity. In the GRASP structure, we observed both canonical and noncanonical binding in the two molecules present in the asymmetric unit making a direct comparison of these binding modes possible. In addition, structures of the PDZ domains from PDLIM1 and PDLIM4 also presented here allow comparison with canonical binding for the PDLIM PDZ domain family. Although influenced by crystal packing arrangements, the structures nevertheless show that changes in the positions of PDZ domain side-chains and the alpha ...Continue Reading

References

Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Jun 8, 1999·Molecular Biology of the Cell·P M GuyG N Gill
Oct 26, 1999·Acta Crystallographica. Section D, Biological Crystallography·A G Leslie
Feb 7, 2001·The Journal of Biological Chemistry·T ValleniusT P Mäkelä
Jun 28, 2002·Molecular Cell·Pascale ZimmermannJan Gettemans
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsThomas C Terwilliger
Mar 3, 2004·Acta Crystallographica. Section D, Biological Crystallography·Laurent C StoroniRandy J Read
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Oct 1, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Torsten W SchulzPavel Osten
Oct 12, 2004·Nature Structural & Molecular Biology·Rhiannon R PenkertKenneth E Prehoda
Oct 27, 2004·Investigative Ophthalmology & Visual Science·Mario TorradoStanislav I Tomarev
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Apr 27, 2005·Cell·Cyril H BenesStephen P Soltoff
Jul 12, 2005·Nature Structural & Molecular Biology·Jia-Fu LongMingjie Zhang
Jun 2, 2006·The Journal of Biological Chemistry·Yingnan ZhangSachdev S Sidhu
Mar 27, 2007·Protein Science : a Publication of the Protein Society·Jonathan M ElkinsDeclan A Doyle
Jul 11, 2007·Biochemistry·Per Jemth, Stefano Gianni
Nov 21, 2007·The International Journal of Neuropsychopharmacology·Chao LiLin He
Dec 18, 2007·Molecular Cell·Hao WuMingjie Zhang
Oct 3, 2008·PLoS Biology·Raffi TonikianSachdev S Sidhu
Mar 3, 2009·Nature Chemical Biology·Yingnan ZhangSachdev S Sidhu

❮ Previous
Next ❯

Citations

Aug 31, 2011·PLoS Computational Biology·Iskra Staneva, Stefan Wallin
Nov 10, 2013·PLoS Computational Biology·Arnab Bhattacherjee, Stefan Wallin
Feb 5, 2013·Journal of Molecular Biology·Thomas M MoonElizabeth J Goldsmith
Oct 3, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Changsuk MoonAnjaparavanda P Naren
Apr 29, 2011·Molecular Systems Biology·David GfellerPhilip M Kim
Aug 27, 2014·Journal of Molecular Biology·Andreas ErnstSachdev S Sidhu
Jul 6, 2011·The Biochemical Journal·Paul D W Eckford, Christine E Bear
May 6, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Santos MañesRosa Ana Lacalle
Dec 2, 2017·Protein Science : a Publication of the Protein Society·Zbigniew Dauter, Mariusz Jaskolski
Apr 22, 2020·Advanced Therapeutics·Nikolaj R ChristensenKristian Strømgaard

❮ 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.