Structural highlights
Function
[CYH1_HUMAN] Promotes guanine-nucleotide exchange on ARF1 and ARF5. Promotes the activation of ARF factors through replacement of GDP with GTP.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Cytohesin-1 (B2-1) is a guanine nucleotide exchange factor for human ADP ribosylation factor (Arf) GTPases, which are important for vesicular protein trafficking and coatamer assembly in the cell. Cytohesin-1 also has been reported to promote cellular adhesion via binding to the beta2 integrin cytoplasmic domain. The solution structure of the Sec7 domain of cytohesin-1, which is responsible for both the protein's guanine nucleotide exchange factor function and beta2 integrin binding, was determined by NMR spectroscopy. The structure consists of 10 alpha-helices that form a unique tertiary fold. The binding between the Sec7 domain and a soluble, truncated version of human Arf-1 was investigated by examining 1H-15N and 1H-13C chemical shift changes between the native protein and the Sec7/Arf-1 complex. We show that the binding to Arf-1 occurs through a large surface on the C-terminal subdomain that is composed of both hydrophobic and polar residues. Structure-based mutational analysis of the cytohesin-1 Sec7 domain has been used to identify residues important for binding to Arf and for mediating nucleotide exchange. Investigations into the interaction between the Sec7 domain and the beta2 integrin cytoplasmic domain suggest that the two proteins do not interact in the solution phase.
Solution structure of the cytohesin-1 (B2-1) Sec7 domain and its interaction with the GTPase ADP ribosylation factor 1.,Betz SF, Schnuchel A, Wang H, Olejniczak ET, Meadows RP, Lipsky BP, Harris EA, Staunton DE, Fesik SW Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7909-14. PMID:9653114[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ogasawara M, Kim SC, Adamik R, Togawa A, Ferrans VJ, Takeda K, Kirby M, Moss J, Vaughan M. Similarities in function and gene structure of cytohesin-4 and cytohesin-1, guanine nucleotide-exchange proteins for ADP-ribosylation factors. J Biol Chem. 2000 Feb 4;275(5):3221-30. PMID:10652308
- ↑ Betz SF, Schnuchel A, Wang H, Olejniczak ET, Meadows RP, Lipsky BP, Harris EA, Staunton DE, Fesik SW. Solution structure of the cytohesin-1 (B2-1) Sec7 domain and its interaction with the GTPase ADP ribosylation factor 1. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7909-14. PMID:9653114
- ↑ Betz SF, Schnuchel A, Wang H, Olejniczak ET, Meadows RP, Lipsky BP, Harris EA, Staunton DE, Fesik SW. Solution structure of the cytohesin-1 (B2-1) Sec7 domain and its interaction with the GTPase ADP ribosylation factor 1. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7909-14. PMID:9653114
