How Does the Proliferating Cell Nuclear Antigen Modulate Binding Specificity to Multiple Partner Proteins?

Journal of Chemical Information and Modeling
Hubert LiNagarajan Vaidehi

Abstract

Proliferating cell nuclear antigen (PCNA) is a member of the family of sliding clamp proteins that serves as a clamp during DNA repair, DNA replication, cell cycle control, and multiple forms of chromatin modification. PCNA functions as a homotrimer and complexes with multiple proteins in order to carry out each of these varied functions. PCNA binds to different partner proteins in the same region of its structure, called the " interdomain connecting loop", but with different affinities. This interdomain connecting loop is an intrinsically disordered region that takes different conformations when binding to different partner proteins. In this work, we performed all-atom molecular dynamics simulations on PCNA trimer unbound to any partner protein, PCNA bound to peptides from different partner proteins, and PCNA bound to the full Fen 1 protein in two different conformations. Using this massive amount of simulation results, we analyzed whether PCNA in its free trimeric form samples conformations that are similar to those when it is bound to different partner proteins. We observed that PCNA samples many of these peptide-bound conformations even when not bound to the peptides and selects specific conformations when binding to partne...Continue Reading

References

Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Jun 19, 1998·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·E Warbrick
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·M A Martí-RenomA Sali
Oct 25, 2000·Protein Science : a Publication of the Protein Society·A FiserA Sali
Dec 26, 2001·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·D DworakowskaJ Jassem
May 24, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·F GrossiA Ardizzoni
Jun 28, 2003·Journal of Cell Science·Giovanni Maga, Ulrich Hubscher
Dec 24, 2004·The EMBO Journal·Shigeru SakuraiToshio Hakoshima
Feb 1, 2005·Proceedings of the National Academy of Sciences of the United States of America·George KontopidisMalcolm D Walkinshaw
Dec 31, 2005·Nucleic Acids Research·Chris StarkMike Tyers
Nov 1, 2006·Protein Science : a Publication of the Protein Society·Min-Yi Shen, Andrej Sali
Nov 23, 2006·Nature Cell Biology·Shao-Chun WangMien-Chie Hung
Dec 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Linda H MalkasRobert J Hickey
Feb 20, 2007·Nucleic Acids Research·Sangeetha VijayakumarAlan E Tomkinson
May 22, 2007·Cell·George-Lucian MoldovanStefan Jentsch
Aug 30, 2008·Cellular and Molecular Life Sciences : CMLS·S N Naryzhny
Mar 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kouta MayanagiKosuke Morikawa
Feb 2, 2010·BMC Structural Biology·Randall McNallyJohn Kuriyan
Jan 20, 2011·Nucleic Acids Research·Doryen BubeckAndrew P Jackson
Apr 8, 2011·Bioinformatics·Ahmet BakanIvet Bahar
May 16, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jordi Querol-AudíIvaylo Ivanov
Jul 21, 2012·Advances in Protein Chemistry and Structural Biology·George AndersonMichael Berk
Nov 10, 2012·PloS One·Alfredo De BiasioFrancisco J Blanco
Apr 13, 2013·Chromosoma·Helle D Ulrich, Tomio Takahashi
Jun 26, 2013·Advances in Protein Chemistry and Structural Biology·Alfredo De Biasio, Francisco J Blanco
Mar 25, 2014·Trends in Pharmacological Sciences·Shao-Chun Wang
Mar 13, 2015·Nature Communications·Alfredo De BiasioFrancisco J Blanco

❮ Previous
Next ❯

Citations


❮ 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.