Structure of the anchor-domain of myristoylated and non-myristoylated HIV-1 Nef protein 1 1Edited by A. R. Fersht

Geyer, Matthias; Munte, Cláudia Elisabeth; Schorr, Jacqueline; Kellner, Roland; Kalbitzer, Hans Robert

doi:10.1006/jmbi.1999.2740

Cited by 99 publications

(93 citation statements)

References 57 publications

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“…Whereas canonical sorting motifs cause the CDs of transmembrane proteins to be recognized constitutively by the endosomal sorting machinery, Nef and the MHC-I ␣ chain may exemplify how an "incomplete" sorting motif enables the transport of a cargo protein to be regulated by a specific CLASP-like molecule that stabilizes its interaction with the coat components of endosomal vesicles. (18,30); the subunit of AP-1 is shown as a ribbon structure, with blue indicating basic, positively charged residues (22); and residues SYSQAAS of the MHC-I CD are green. Key residues in Nef, the MHC-I CD, and 1 are indicated.…”

Section: Vol 82 2008mentioning

confidence: 99%

Cooperative Binding of the Class I Major Histocompatibility Complex Cytoplasmic Domain and Human Immunodeficiency Virus Type 1 Nef to the Endosomal AP-1 Complex via Its μ Subunit

Noviello

Bénichou

Guatelli

2008

J Virol

122

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Section: Vol 82 2008mentioning

confidence: 99%

Cooperative Binding of the Class I Major Histocompatibility Complex Cytoplasmic Domain and Human Immunodeficiency Virus Type 1 Nef to the Endosomal AP-1 Complex via Its μ Subunit

Noviello

Bénichou

Guatelli

2008

J Virol

122

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“…Additionally, the structure of the N-terminal anchor domain has been solved using NMR spectroscopy, and it appears that this domain adopts a relatively unstructured conformation that becomes partially ordered upon the addition of an N-terminal myristyl group (57). Geyer and colleagues used these known structures to assemble a structural prediction of the conformation of the full-length Nef polypeptide (58).…”

Section: General Properties Of Hiv-1 and Siv Nef Proteinsmentioning

confidence: 99%

Human Immunodeficiency Virus Type 1 Nef: Adapting to Intracellular Trafficking Pathways

Roeth¹,

Collins

2006

Microbiol Mol Biol Rev

168

156

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SUMMARY The Nef protein of primate lentiviruses is a unique protein that has evolved in several ways to manipulate the biology of an infected cell to support viral replication, immune evasion, pathogenesis, and viral spread. Nef is a small (25- to 34-kDa), myristoylated protein that binds to a collection of cellular factors and acts as an adaptor to generate novel protein interactions to accomplish specific functions. Of the many biological activities attributed to Nef, the reduction of surface levels of the viral receptor (CD4) and antigen-presenting molecules (major histocompatibility complex class I) has been intensely examined; recent evidence demonstrates that Nef utilizes multiple, distinct pathways to affect these proteins. To accomplish this, Nef promotes the formation of multiprotein complexes, recruiting host adaptor proteins to commandeer intracellular vesicular trafficking routes. The altered trafficking of several other host molecules has also been reported, and an emerging theory suggests that Nef generates pleiotrophic effects in the secretory and endocytic pathways that reprogram intracellular protein trafficking and may ultimately provide an efficient platform for viral assembly. This review critically discusses some of the major findings regarding the impact of human immunodeficiency virus type 1 Nef on host protein transport and addresses some emerging directions in this area of human immunodeficiency virus biology.

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“…NMR spectra were converted to Bruker format and processed with XWINNMR and evaluated and plotted with Aurelia (35). The assignment strategy was based on the identification of individual resonance spin systems from homonuclear TOCSY experiments following the sequential path with homonuclear two-dimensional and 15 N-separated three-dimensional NOESY spectra similarly are described (36).…”

Section: Nmr Spectroscopy-nmr Experiments With Homonuclear Ormentioning

confidence: 99%

Biochemical Characterization of the Diaphanous Autoregulatory Interaction in the Formin Homology Protein FHOD1

Schönichen

Alexander

Gasteier

et al. 2006

Journal of Biological Chemistry

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Diaphanous related formins (DRFs) are cytoskeleton remodeling proteins that mediate specific upstream GTPase signals to regulate cellular processes such as cytokinesis, cell polarity, and organelle motility. Previous work on the Rho-interacting DRF mDia has established that the biological activity of DRFs is regulated by an autoinhibitory interaction of a C-terminal diaphanous autoregulatory domain (DAD) with the DRF N terminus. This autoinhibition is released upon competitive binding of an activated GTPase to the N terminus of the DRF. Analyzing autoregulation of the Rac1-interacting DRF FHOD1, we utilized in vitro binding studies to identify a 60-amino acid DAD at the protein C terminus that recognizes an N-terminal formin homology (FH) 3 domain. Importantly, the FH3 domain of FHOD1 does not overlap with the proposed Rac1-binding domain. The FHOD1 DAD was found to contain one functional hydrophobic autoregulatory motif, while a previously uncharacterized basic cluster that is conserved in all DRF family DADs also contributed to the FH3-DAD interaction. Simultaneous mutation of both motifs efficiently released autoinhibition of FHOD1 in NIH3T3 cells resulting in the formation of actin stress fibers and increased serum response element transcription. A second putative hydrophobic autoregulatory motif N-terminal of the DAD belongs to a unique FHOD subdomain of yet undefined function. NMR structural analysis and size exclusion chromatography experiments revealed that the FHOD1 DAD is intrinsically unstructured with a tendency for a helical conformation in the hydrophobic autoregulation motif. Together, these data suggest that in FHOD1, DAD acts as signal sequence for binding to the well folded and monomeric FH3 domain and imply an activation mechanism that differs from competitive binding of Rac1 and DAD to one interaction site.Formin proteins are involved in the regulation of many cytoskeletal processes including cytokinesis, actin cable and stress fiber formation, polarity establishment, neurite outgrowth, and intracellular trafficking (reviewed in Refs. 1 and 2). These functions are achieved by their ability to promote F-actin assembly at the filament barbed end and to move processively with the barbed end as it elongates (3-7). Formins are large proteins of typically more than 1000 amino acids that are defined by the presence of two conserved regions, namely the formin homology 1 and 2 (FH1 and FH2) 2 domains (1). Additional conserved domains such as a N-terminal GTPase-binding domain (GBD) and a C-terminal diaphanous autoregulation domain (DAD) were found to constitute a formin subfamily, the diaphanous related formins (DRFs) (8). Over the last years, DRFs have emerged as a group of proteins with the potential to bridge between G-protein signals and the cytoskeleton via their ability to bind activated small GTPases and to subsequently remodel the cytoskeleton (9 -13).At present, phylogenetic analyses of FH2 domains suggest that metazoan formins fall into seven groups, termed Dia (diaphanous), DAAM (dishevelle...

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Structure of the anchor-domain of myristoylated and non-myristoylated HIV-1 Nef protein 1 1Edited by A. R. Fersht

Cited by 99 publications

References 57 publications

Cooperative Binding of the Class I Major Histocompatibility Complex Cytoplasmic Domain and Human Immunodeficiency Virus Type 1 Nef to the Endosomal AP-1 Complex via Its μ Subunit

Cooperative Binding of the Class I Major Histocompatibility Complex Cytoplasmic Domain and Human Immunodeficiency Virus Type 1 Nef to the Endosomal AP-1 Complex via Its μ Subunit

Human Immunodeficiency Virus Type 1 Nef: Adapting to Intracellular Trafficking Pathways

Biochemical Characterization of the Diaphanous Autoregulatory Interaction in the Formin Homology Protein FHOD1

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