Modular type I polyketide synthase acyl carrier protein domains share a common N-terminally extended fold

Scientific Reports
Luisa MorettoR William Broadhurst

Abstract

Acyl carrier protein (ACP) domains act as interaction hubs within modular polyketide synthase (PKS) systems, employing specific protein-protein interactions to present acyl substrates to a series of enzyme active sites. Many domains from the multimodular PKS that generates the toxin mycolactone display an unusually high degree of sequence similarity, implying that the few sites which vary may do so for functional reasons. When domain boundaries based on prior studies were used to prepare two isolated ACP segments from this system for studies of their interaction properties, one fragment adopted the expected tertiary structure, but the other failed to fold, despite sharing a sequence identity of 49%. Secondary structure prediction uncovered a previously undetected helical region (H0) that precedes the canonical helix-bundle ACP topology in both cases. This article reports the NMR solution structures of two N-terminally extended mycolactone mACP constructs, mH0ACPa and mH0ACPb, both of which possess an additional α-helix that behaves like a rigid component of the domain. The interactions of these species with a phosphopantetheinyl transferase and a ketoreductase domain are unaffected by the presence of H0, but a shorter construct...Continue Reading

References

Jan 1, 1994·Protein Science : a Publication of the Protein Society·L A HorvathJ H Prestegard
Jan 20, 1993·Journal of Molecular Biology·A A Adzhubei, M J Sternberg
May 8, 1998·Journal of Magnetic Resonance·M OttigerA Bax
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·S C TsaiR M Stroud
Jan 23, 2004·Proceedings of the National Academy of Sciences of the United States of America·Timothy P StinearStewart T Cole
Jun 3, 2004·Genome Research·Gavin E CrooksSteven E Brenner
Jun 25, 2004·Nucleic Acids Research·Mohd Zeeshan AnsariDebasisa Mohanty
Aug 26, 2004·PLoS Biology·Eugene HurRobert J Fletterick
Oct 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jun YinChristopher T Walsh
Dec 3, 2005·Nature Reviews. Microbiology·Kira J Weissman, Peter F Leadlay
Mar 2, 2006·Journal of the American Chemical Society·Alice Y ChenChaitan Khosla
Dec 23, 2006·Proteins·Aneerban BhattacharyaGaetano T Montelione
Jul 27, 2007·Natural Product Reports·Andrew C Mercer, Michael D Burkart
Jul 28, 2007·Chemistry & Biology·Alice Y ChenChaitan Khosla
Sep 26, 2007·Protein Science : a Publication of the Protein Society·Viktor Y AlekseyevChaitan Khosla
Jan 4, 2008·Protein Expression and Purification·Susanne GräslundJohan Weigelt
Dec 17, 2008·BMC Bioinformatics·Shashi Bhushan Pandit, Jeffrey Skolnick
Jul 22, 2009·Phytochemistry·Holger Jenke-Kodama, Elke Dittmann
Dec 18, 2009·Journal of Magnetic Resonance·Ming-Sin CheungR William Broadhurst
Dec 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Shiven KapurChaitan Khosla
Mar 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Shiven KapurChaitan Khosla
Aug 4, 2012·Natural Product Reports·Adrian T Keatinge-Clay
Aug 30, 2012·Natural Product Reports·John Crosby, Matthew P Crump
Oct 31, 2013·Journal of Biomolecular NMR·Konstantin BerlinDavid Fushman
Nov 10, 2013·Methods in Molecular Biology·Yuanpeng Janet HuangGaetano T Montelione
Jun 27, 2014·Nature·Jonathan R WhicherGeorgios Skiniotis
Oct 15, 2014·Natural Product Reports·Kira J Weissman
Apr 8, 2015·Nucleic Acids Research·Weizhong LiRodrigo Lopez
Nov 17, 2015·Chemical Communications : Chem Comm·Constance B BaileyAdrian T Keatinge-Clay
Nov 20, 2015·Natural Product Reports·Adrian T Keatinge-Clay
Dec 18, 2015·Nucleic Acids Research·Robert D FinnAlex Bateman
Apr 28, 2016·The Journal of Antibiotics·Matthew P OstrowskiChaitan Khosla
Jun 9, 2016·Current Opinion in Structural Biology·Thomas RobbinsChaitan Khosla

❮ Previous
Next ❯

Citations

Apr 13, 2021·Proteins·Melissa HirschAdrian T Keatinge-Clay

❮ Previous
Next ❯

Methods Mentioned

BETA
isothermal titration calorimetry
nuclear magnetic resonance
size exclusion chromatography
circular dichroism
NMR
size

Software Mentioned

ARIA
Azara
LAARLAGL
Scratch
align
MUSCLE
PyMOL
WebLogo
GREMLIN
frTM

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.