1BC9

CYTOHESIN-1/B2-1 SEC7 DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE

Summary for 1BC9

• Entry DOI: 10.2210/pdb1bc9/pdb
• Descriptor: CYTOHESIN-1 (1 entity in total)
• Functional Keywords: exchange factor, integrin binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 23388.76

Authors

Betz, S.F.,Schnuchel, A.,Wang, H.,Olejniczak, E.T.,Meadows, R.P.,Fesik, S.W. (deposition date: 1998-05-06, release date: 1999-05-11, Last modification date: 2024-05-22)

Primary citation

Betz, S.F.,Schnuchel, A.,Wang, H.,Olejniczak, E.T.,Meadows, R.P.,Lipsky, B.P.,Harris, E.A.,Staunton, D.E.,Fesik, S.W.
Solution structure of the cytohesin-1 (B2-1) Sec7 domain and its interaction with the GTPase ADP ribosylation factor 1.
Proc.Natl.Acad.Sci.USA, 95:7909-7914, 1998

PubMed Abstract: 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.

PubMed: 9653114
DOI: 10.1073/pnas.95.14.7909

Experimental method

SOLUTION NMR