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PDBsum entry 1bc9
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Exchange factor
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PDB id
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1bc9
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References listed in PDB file
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Key reference
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Title
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Solution structure of the cytohesin-1 (b2-1) sec7 domain and its interaction with the gtpase ADP ribosylation factor 1.
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Authors
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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.
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Ref.
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Proc Natl Acad Sci U S A, 1998,
95,
7909-7914.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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