1avz
From Proteopedia
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| - | [[Image:1avz.gif|left|200px]] | + | [[Image:1avz.gif|left|200px]] |
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| - | '''V-1 NEF PROTEIN IN COMPLEX WITH WILD TYPE FYN SH3 DOMAIN''' | + | {{Structure |
| + | |PDB= 1avz |SIZE=350|CAPTION= <scene name='initialview01'>1avz</scene>, resolution 3.0Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] | ||
| + | |GENE= HIV-1 NEF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]), FYN TYROSINE KINASE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''V-1 NEF PROTEIN IN COMPLEX WITH WILD TYPE FYN SH3 DOMAIN''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1AVZ is a [ | + | 1AVZ is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AVZ OCA]. |
==Reference== | ==Reference== | ||
| - | The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling., Arold S, Franken P, Strub MP, Hoh F, Benichou S, Benarous R, Dumas C, Structure. 1997 Oct 15;5(10):1361-72. PMID:[http:// | + | The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling., Arold S, Franken P, Strub MP, Hoh F, Benichou S, Benarous R, Dumas C, Structure. 1997 Oct 15;5(10):1361-72. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9351809 9351809] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
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[[Category: tyrosine kinase]] | [[Category: tyrosine kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:03:05 2008'' |
Revision as of 08:03, 20 March 2008
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| , resolution 3.0Å | |||||||
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| Gene: | HIV-1 NEF (Human immunodeficiency virus 1), FYN TYROSINE KINASE (Homo sapiens) | ||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
V-1 NEF PROTEIN IN COMPLEX WITH WILD TYPE FYN SH3 DOMAIN
Overview
BACKGROUND: Human immunodeficiency virus (HIV) Nef protein accelerates virulent progression of acquired immunodeficiency syndrome (AIDS) by its interaction with specific cellular proteins involved in signal transduction and host cell activation. Nef has been shown to bind specifically to a subset of the Src family of kinases. The structures of free Nef and Nef bound to Src homology region 3 (SH3) domain are important for the elucidation of how the affinity and specificity for the Src kinase family SH3 domains are achieved, and also for the development of potential drugs and vaccines against AIDS. RESULTS: We have determined the crystal structures of the conserved core of HIV-1 Nef protein alone and in complex with the wild-type SH3 domain of the p59fyn protein tyrosine kinase (Fyn), at 3.0 A resolution. Comparison of the bound and unbound Nef structures revealed that a proline-rich motif (Pro-x-x-Pro), which is implicated in SH3 binding, is partially disordered in the absence of the binding partner; this motif only fully adopts a left-handed polyproline type II helix conformation upon complex formation with the Fyn SH3 domain. In addition, the structures show how an arginine residue (Arg77) of Nef interacts with Asp 100 of the so-called RT loop within the Fyn SH3 domain, and triggers a hydrogen-bond rearrangement which allows the loop to adapt to complement the Nef surface. The Arg96 residue of the Fyn SH3 domain is specifically accommodated in the same hydrophobic pocket of Nef as the isoleucine residue of a previously described Fyn SH3 (Arg96-->lle) mutant that binds to Nef with higher affinity than the wild type. CONCLUSIONS: The three-dimensional structures support evidence that the Nef-Fyn complex forms in vivo and may have a crucial role in the T cell perturbating action of Nef by altering T cell receptor signaling. The structures of bound and unbound Nef reveal that the multivalency of SH3 binding may be achieved by a ligand induced flexibility in the RT loop. The structures suggest possible targets for the design of inhibitors which specifically block Nef-SH3 interactions.
About this Structure
1AVZ is a Protein complex structure of sequences from Homo sapiens and Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling., Arold S, Franken P, Strub MP, Hoh F, Benichou S, Benarous R, Dumas C, Structure. 1997 Oct 15;5(10):1361-72. PMID:9351809
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