PDBsum entry 1bc9

Exchange factor

PDB id: 1bc9

Contents

Protein chain

200 a.a. *

* Residue conservation analysis

PDB id:

1bc9

Name:

Exchange factor

Title:

Cytohesin-1/b2-1 sec7 domain, nmr, minimized average structure

Structure:

Cytohesin-1. Chain: a. Fragment: sec7 domain,. Synonym: b2-1, sec7 homolog b2-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Organ: spleen. Gene: b2-1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

1 models

Authors:

S.F.Betz,A.Schnuchel,H.Wang,E.T.Olejniczak,R.P.Meadows,S.W.Fesik

Key ref:

S.F.Betz et al. (1998). 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, 95, 7909-7914. PubMed id: 9653114 DOI: 10.1073/pnas.95.14.7909

Date:

06-May-98 Release date: 11-May-99

Protein chain

Q15438  (CYH1_HUMAN) -  Cytohesin-1 from Homo sapiens

Seq: 398 a.a.

Struc: 200 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1073/pnas.95.14.7909

Proc Natl Acad Sci U S A 95:7909-7914 (1998)

PubMed id: 9653114

Solution structure of the cytohesin-1 (B2-1) Sec7 domain and its interaction with the GTPase ADP ribosylation factor 1.

S.F.Betz, A.Schnuchel, H.Wang, E.T.Olejniczak, R.P.Meadows, B.P.Lipsky, E.A.Harris, D.E.Staunton, S.W.Fesik.

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.

Selected figure(s)

Figure 3.
Fig. 3. PROCHECK-NMR-generated (35) Ramachandran plot for the energy minimized, average structure of the cytohesin-1 Sec7 domain. Residues with geometries outside of acceptable regions are indicated. Shaded areas marked by uppercase, lowercase, and lowercase residues with a "~" prefix refer to most favored, favored, and allowed backbone geometries, respectively.

Figure 5.
Fig. 5. MOLSCRIPT (39) diagram of the structure of the cytohesin-1 Sec7 domain. The N-terminal subdomain (residues 58-135) is shaded in dark gray, and the C-terminal subdomain (residues 136-248) is shown in light gray. The unstructured polyhistidine tag at the C terminus has been excluded for clarity.

Figures were selected by an automated process.