Structural, Biochemical, and  in Vivo  Characterization of the First Virally Encoded Cyclophilin from the Mimivirus

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Although multiple viruses utilize host cell cyclophilins, including severe acute respiratory syndrome (SARS) and human immunodeficiency virus type-1(HIV-1), their role in infection is poorly understood. To help elucidate these roles, we have characterized the first virally encoded cyclophilin (mimicyp) derived from the largest virus discovered to date (the Mimivirus) that is also a causative agent of pneumonia in humans. Mimicyp adopts a typical cyclophilin-fold, yet it also forms trimers unlike any previously characterized homologue. Strikingly, immunofluorescence assays reveal that mimicyp localizes to the surface of the mature virion, as recently proposed for several viruses that recruit host cell cyclophilins such as SARS and HIV-1. Additionally mimicyp lacks peptidyl-prolyl isomerase activity in contrast to human cyclophilins. Thus, this study suggests that cyclophilins, whether recruited from host cells (i.e. HIV-1 and SARS) or virally encoded (i.e. Mimivirus), are localized on viral surfaces for at least a subset of viruses.

Related collections

Most cited references 63

Record: found
Abstract: found
Article: not found

The 1.2-megabase genome sequence of Mimivirus.

Didier Raoult, Stéphane Audic, Catherine Robert … (2004)

We recently reported the discovery and preliminary characterization of Mimivirus, the largest known virus, with a 400-nanometer particle size comparable to mycoplasma. Mimivirus is a double-stranded DNA virus growing in amoebae. We now present its 1,181,404-base pair genome sequence, consisting of 1262 putative open reading frames, 10% of which exhibit a similarity to proteins of known functions. In addition to exceptional genome size, Mimivirus exhibits many features that distinguish it from other nucleocytoplasmic large DNA viruses. The most unexpected is the presence of numerous genes encoding central protein-translation components, including four amino-acyl transfer RNA synthetases, peptide release factor 1, translation elongation factor EF-TU, and translation initiation factor 1. The genome also exhibits six tRNAs. Other notable features include the presence of both type I and type II topoisomerases, components of all DNA repair pathways, many polysaccharide synthesis enzymes, and one intein-containing gene. The size and complexity of the Mimivirus genome challenge the established frontier between viruses and parasitic cellular organisms. This new sequence data might help shed a new light on the origin of DNA viruses and their role in the early evolution of eukaryotes.

0 comments Cited 314 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Intrinsic dynamics of an enzyme underlies catalysis.

Elan Z. Eisenmesser, Oscar Millet, Wladimir Labeikovsky … (2005)

A unique feature of chemical catalysis mediated by enzymes is that the catalytically reactive atoms are embedded within a folded protein. Although current understanding of enzyme function has been focused on the chemical reactions and static three-dimensional structures, the dynamic nature of proteins has been proposed to have a function in catalysis. The concept of conformational substates has been described; however, the challenge is to unravel the intimate linkage between protein flexibility and enzymatic function. Here we show that the intrinsic plasticity of the protein is a key characteristic of catalysis. The dynamics of the prolyl cis-trans isomerase cyclophilin A (CypA) in its substrate-free state and during catalysis were characterized with NMR relaxation experiments. The characteristic enzyme motions detected during catalysis are already present in the free enzyme with frequencies corresponding to the catalytic turnover rates. This correlation suggests that the protein motions necessary for catalysis are an intrinsic property of the enzyme and may even limit the overall turnover rate. Motion is localized not only to the active site but also to a wider dynamic network. Whereas coupled networks in proteins have been proposed previously, we experimentally measured the collective nature of motions with the use of mutant forms of CypA. We propose that the pre-existence of collective dynamics in enzymes before catalysis is a common feature of biocatalysts and that proteins have evolved under synergistic pressure between structure and dynamics.

0 comments Cited 227 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid.

D K Worthylake, Wesley Sundquist, Jennifer R Gamble … (1996)

The HIV-1 capsid protein forms the conical core structure at the center of the mature virion. Capsid also binds the human peptidyl prolyl isomerase, cyclophilin A, thereby packaging the enzyme into the virion. Cyclophilin A subsequently performs an essential function in HIV-1 replication, possibly helping to disassemble the capsid core upon infection. We report the 2.36 A crystal structure of the N-terminal domain of HIV-1 capsid (residues 1-151) in complex with human cyclophilin A. A single exposed capsid loop (residues 85-93) binds in the enzyme's active site, and Pro-90 adopts an unprecedented trans conformation. The structure suggests how cyclophilin A can act as a sequence-specific binding protein and a nonspecific prolyl isomerase. In the crystal lattice, capsid molecules assemble into continuous planar strips. Side by side association of these strips may allow capsid to form the surface of the viral core. Cyclophilin A could then function by weakening the association between capsid strips, thereby promoting disassembly of the viral core.

0 comments Cited 158 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Elan Z. Eisenmesser

Journal

Journal ID (nlm-ta): J Mol Biol

Journal ID (iso-abbrev): J. Mol. Biol

Title: Journal of Molecular Biology

Publisher: Elsevier

ISSN (Print): 0022-2836

ISSN (Electronic): 1089-8638

Publication date PMC-release: 29 August 2007

Publication date (Print): 18 April 2008

Publication date (Electronic): 29 August 2007

Volume: 378

Issue: 1

Pages: 71-86

Affiliations

[1 ]Department of Biochemistry & Molecular Genetics, University of Colorado Health Science Center, School of Medicine, 12801 E 17 ^th Ave, Aurora, CO 80045, USA

[2 ]Department of Biochemistry, Brandeis University and Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA

[3 ]Unité des Rickettsies, Faculté de Médecine, CNRSUMR6020, Université de la Méditerranée, 13385 Marseille Cedex 05, France

[4 ]Department of Chemistry & Biochemistry, University of Colorado at Boulder, Boulder, CO 80309, USA

[5 ]Structural Genomics Consortium and the Department of Physiology, University of Toronto, 100 College St., Toronto, ON, Canada M5G1L5

Author notes

[* ]Corresponding author. Elan.Eisenmesser@ 123456UCHSC.edu

Article

Publisher ID: S0022-2836(07)01132-1

DOI: 10.1016/j.jmb.2007.08.051

PMC ID: 2884007

PubMed ID: 18342330

SO-VID: efff4c93-0783-4980-82c6-c293ce764dfe

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

History

Date received : 28 March 2007

Date revision received : 22 August 2007

Date accepted : 23 August 2007

Comments

Comment on this article

scite_

Cited by 15

See all cited by

Most referenced authors 1,133

See all reference authors

- Version 1

Structural, Biochemical, and in Vivo Characterization of the First Virally Encoded Cyclophilin from the Mimivirus

Read this article at

Abstract

Related collections

Coronaviruses, COVID-19 and SARS-CoV-2

Most cited references 63

The 1.2-megabase genome sequence of Mimivirus.

Intrinsic dynamics of an enzyme underlies catalysis.

Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 646

Cited by 15

Most referenced authors 1,133