Evidence for a mechanism by which omega-3 polyunsaturated lipids may affect membrane protein function.

Authors:
Dr. Mauricio Carrillo-Tripp, PhD
Dr. Mauricio Carrillo-Tripp, PhD
Biomolecular Diversity Laboratory, Cinvestav
Associate Profesor
Computational Biophysics
Irapuato, Guanajuato | México
Scott E Feller
Scott E Feller
Wabash College
United States

Biochemistry 2005 Aug;44(30):10164-9

Department of Chemistry, Wabash College, 301 West Wabash Avenue, Crawfordsville, Indiana 47933, USA.

We have calculated the lateral pressure profile from well-converged, experimentally validated, molecular dynamics simulations of hydrated lipid bilayer membranes containing highly polyunsaturated fatty acids. The three simulations, each 30 ns in length, contain omega-3 fatty acids, omega-6 fatty acids, and a mixture of omega-3 fatty acids and cholesterol and were continued from previously published simulations that demonstrated excellent agreement with a wide variety of experimental measurements. We find that the distribution of lateral stress within the hydrophobic core of the membrane is sensitively dependent on the degree of chain unsaturation and on the presence of cholesterol. Replacing omega-3 fatty acids with omega-6 chains, or incorporating cholesterol into the membrane, shifts the repulsive lateral chain pressure away from the lipid/water interface toward the bilayer interior. This may support a previously proposed mechanism by which lipid composition may affect conformational equilibrium for integral membrane proteins.

Download full-text PDF

Source
http://dx.doi.org/10.1021/bi050822eDOI Listing

Still can't find the full text of the article?

Sign up to send a request to the authors directly.
August 2005
22 Reads
22 PubMed Central Citations(source)
3.02 Impact Factor

Publication Analysis

Top Keywords

fatty acids
20
omega-3 fatty
12
acids omega-6
8
acids
5
fatty
5
excellent agreement
4
demonstrated excellent
4
bilayer interior
4
simulations demonstrated
4
interface bilayer
4
lipid/water interface
4
wide variety
4
variety experimental
4
published simulations
4
agreement wide
4
acids cholesterol
4
support proposed
4
omega-6 fatty
4
omega-6 chains
4
simulations length
4

Similar Publications

Cryptic sequence features in the active postmortem transcriptome.

BMC Genomics 2018 Sep 14;19(1):675. Epub 2018 Sep 14.

City of Hope, Information Sciences - Beckman Research Institute, 4920 Rivergrade Rd., Irwindale, CA, 91706, USA.

Background: Our previous study found that more than 500 transcripts significantly increased in abundance in the zebrafish and mouse several hours to days postmortem relative to live controls. The current literature suggests that most mRNAs are post-transcriptionally regulated in stressful conditions. We rationalized that the postmortem transcripts must contain sequence features (3- to 9- mers) that are unique from those in the rest of the transcriptome and that these features putatively serve as binding sites for proteins and/or non-coding RNAs involved in post-transcriptional regulation. Read More

View Article
September 2018
42 Reads
3.99 Impact Factor

Direct observation of Medicaid beneficiary attempts to fill prescriptions for nicotine replacement medications.

J Am Pharm Assoc (2003) 2018 Jul - Aug;58(4):432-437. Epub 2018 Apr 22.

Objectives: Although many states have expanded Medicaid coverage of cessation medications, utilization remains low. Anecdotal reports suggest that beneficiaries are at times denied coverage of cessation medications at the pharmacy counter. We conducted an observational community-wide case study of Medicaid beneficiary attempts to fill over-the-counter nicotine replacement therapy at pharmacies. Read More

View Article
April 2018
40 Reads

Chemical reaction dynamics.

Chem Soc Rev 2017 Dec;46(24):7481-7482

State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

View Article
December 2017
37 Reads
33.38 Impact Factor

Activity of 2-(quinolin-4-yloxy)acetamides in Mycobacterium tuberculosis clinical isolates and identification of their molecular target by whole-genome sequencing.

Int J Antimicrob Agents 2018 Mar 23;51(3):378-384. Epub 2017 Aug 23.

Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Av. Ipiranga 6681 - Prédio 92A Tecnopuc, Porto Alegre, RS 90619-900, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, Brazil.

The 2-(quinolin-4-yloxy)acetamides (QOAs) have been reported to be promising molecules for tuberculosis treatment. Recent studies demonstrated their potent antimycobacterial activity, biological stability and synergism with rifampicin. The identification of the molecular target is an essential step towards the development of a novel drug candidate. Read More

View Article
March 2018
62 Reads
2 PubMed Central Citations(source)
4.30 Impact Factor

Covalent inhibition of protein tyrosine phosphatases.

Mol Biosyst 2017 Jun;13(7):1257-1279

Department of Medicinal Chemistry and Molecular Pharmacology, Department of Chemistry, Center for Cancer Research, and Institute for Drug Discovery, Purdue University, 720 Clinic Drive, West Lafayette, IN 47907, USA.

Protein tyrosine phosphatases (PTPs) are a large family of 107 signaling enzymes that catalyze the hydrolytic removal of phosphate groups from tyrosine residues in a target protein. The phosphorylation status of tyrosine residues on proteins serve as a ubiquitous mechanism for cellular signal transduction. Aberrant function of PTPs can lead to many human diseases, such as diabetes, obesity, cancer, and autoimmune diseases. Read More

View Article
June 2017
57 Reads