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Structural libraries of protein models for multiple species to understand evolution of the renin-angiotensin system. Gen Comp Endocrinol 2015 May 01;215:106-16

Date

09/28/2014

Pubmed ID

25260253

Pubmed Central ID

PMC4375088

DOI

10.1016/j.ygcen.2014.09.010

Scopus ID

2-s2.0-84939957085   1 Citation

Abstract

The details of protein pathways at a structural level provides a bridge between genetics/molecular biology and physiology. The renin-angiotensin system is involved in many physiological pathways with informative structural details in multiple components. Few studies have been performed assessing structural knowledge across the system. This assessment allows use of bioinformatics tools to fill in missing structural voids. In this paper we detail known structures of the renin-angiotensin system and use computational approaches to estimate and model components that do not have their protein structures defined. With the subsequent large library of protein structures, we then created a species specific protein library for human, mouse, rat, bovine, zebrafish, and chicken for the system. The rat structural system allowed for rapid screening of genetic variants from 51 commonly used rat strains, identifying amino acid variants in angiotensinogen, ACE2, and AT1b that are in contact positions with other macromolecules. We believe the structural map will be of value for other researchers to understand their experimental data in the context of an environment for multiple proteins, providing pdb files of proteins for the renin-angiotensin system in six species. With detailed structural descriptions of each protein, it is easier to assess a species for use in translating human diseases with animal models. Additionally, as whole genome sequencing continues to decrease in cost, tools such as molecular modeling will gain use as an initial step in designing efficient hypothesis driven research, addressing potential functional outcomes of genetic variants with precompiled protein libraries aiding in rapid characterizations.

Author List

Prokop JW, Petri V, Shimoyama ME, Watanabe IK, Casarini DE, Leeper TC, Bilinovich SM, Jacob HJ, Santos RA, Martins AS, Araujo FC, Reis FM, Milsted A

Author

Mary E. Shimoyama PhD Associate Professor in the Biomedical Engineering department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Angiotensinogen
Animals
Biological Evolution
Cattle
Chickens
Computational Biology
Humans
Mice
Models, Molecular
Molecular Sequence Data
Protein Conformation
Rats
Renin
Renin-Angiotensin System
Sequence Homology, Amino Acid
Species Specificity
Zebrafish
jenkins-FCD Prod-387 b0ced2662056320369de4e5cd5f21c218c03feb3