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2abo

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[[Image:2abo.gif|left|200px]]
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{{STRUCTURE_2abo| PDB=2abo | SCENE= }}
{{STRUCTURE_2abo| PDB=2abo | SCENE= }}
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'''NMR structure of gamma herpesvirus 68 a viral Bcl-2 homolog'''
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===NMR structure of gamma herpesvirus 68 a viral Bcl-2 homolog===
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==Overview==
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Antiapoptotic Bcl-2 family proteins inhibit apoptosis in cultured cells by binding BH3 domains of proapoptotic Bcl-2 family members via a hydrophobic BH3 binding groove on the protein surface. We investigated the physiological importance of the BH3 binding groove of an antiapoptotic Bcl-2 protein in mammals in vivo by analyzing a viral Bcl-2 family protein. We show that the gamma-herpesvirus 68 (gammaHV68) Bcl-2 family protein (gammaHV68 v-Bcl-2), which is known to inhibit apoptosis in cultured cells, inhibits both apoptosis in primary lymphocytes and Bax toxicity in yeast. Nuclear magnetic resonance determination of the gammaHV68 v-Bcl-2 structure revealed a BH3 binding groove that binds BH3 domain peptides from proapoptotic Bcl-2 family members Bax and Bak via a molecular mechanism shared with host Bcl-2 family proteins, involving a conserved arginine in the BH3 peptide binding groove. Mutations of this conserved arginine and two adjacent amino acids to alanine (SGR to AAA) within the BH3 binding groove resulted in a properly folded protein that lacked the capacity of the wild-type gammaHV68 v-Bcl-2 to bind Bax BH3 peptide and to block Bax toxicity in yeast. We tested the physiological importance of this v-Bcl-2 domain during viral infection by engineering viral mutants encoding a v-Bcl-2 containing the SGR to AAA mutation. This mutation resulted in a virus defective for both efficient reactivation of gammaHV68 from latency and efficient persistent gammaHV68 replication. These studies demonstrate an essential functional role for amino acids in the BH3 peptide binding groove of a viral Bcl-2 family member during chronic infection.
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(as it appears on PubMed at http://www.pubmed.gov), where 16201011 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16201011}}
==About this Structure==
==About this Structure==
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2ABO is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Murid_herpesvirus_4 Murid herpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ABO OCA].
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2ABO is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Murid_herpesvirus_4 Murid herpesvirus 4]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ABO OCA].
==Reference==
==Reference==
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[[Category: Murine gamma herpes virus]]
[[Category: Murine gamma herpes virus]]
[[Category: Viral bcl-2 homolog]]
[[Category: Viral bcl-2 homolog]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:51:24 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:23:19 2008''

Revision as of 00:23, 28 July 2008

Image:2abo.png

Template:STRUCTURE 2abo

NMR structure of gamma herpesvirus 68 a viral Bcl-2 homolog

Template:ABSTRACT PUBMED 16201011

About this Structure

2ABO is a Single protein structure of sequence from Murid herpesvirus 4. Full experimental information is available from OCA.

Reference

A surface groove essential for viral Bcl-2 function during chronic infection in vivo., Loh J, Huang Q, Petros AM, Nettesheim D, van Dyk LF, Labrada L, Speck SH, Levine B, Olejniczak ET, Virgin HW 4th, PLoS Pathog. 2005 Sep;1(1):e10. Epub 2005 Sep 30. PMID:16201011

Page seeded by OCA on Mon Jul 28 03:23:19 2008

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