| Literature References | 1. NISHIMURA, N., GOJI, J., NAKAMURA, H., ORITA, S., TAKAI, Y. AND SANO, K.
Cloning of a brain-type isoform of human Rab GDI and its expression in
human neuroblastoma cell lines and tumor specimens.
CANCER RES. 55 5445-5450 (1995).
2. SCHALK, I., ZENG, K., WU, S.K., STURA, E.A., MATTESON, J., HUANG, M.,
TANDON, A., WILSON, I.A. AND BALCH, W.E.
Structure and mutational analysis of Rab GDP-dissociation inhibitor.
NATURE 381 42-48 (1996).
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| Documentation | Rab proteins, a family of small Ras-related GTP-binding proteins, are
involved in regulation of intracellular vesicle trafficking [1]. Rab GDP
dissociation inhibitor (GDI) forms a soluble complex with Rab proteins,
thereby preventing exchange of GDP for GTP. Rab GDI exists in several
isoforms, and belongs to the TCD/MRS6 family of GDP dissociation inhibitors.
The crystal structure of the bovine alpha-isoform of Rab GDI has been
determined to a resolution of 1.81A [2]. The protein is composed of two
main structural units: a large complex multi-sheet domain I, and a smaller
alpha-helical domain II.
The structural organisation of domain I is closely related to FAD-containing
monooxygenases and oxidases [2]. Conserved regions common to GDI and the
choroideraemia gene product (or Rab escort protein), which delivers Rab to
catalytic subunits of Rab geranylgeranyltransferase II, are clustered on
one face of the domain [2]. The two most conserved regions form a compact
structure at the apex of the molecule; site-directed mutagenesis has shown
these regions to play a critical role in the binding of Rab proteins [2].
RABGDI is a 9-element fingerprint that provides a signature for Rab GDP
dissociation inhibitors. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from short conserved
sections spanning the central portion of the alignment, focusing on those
regions that characterise the RAB GDI proteins but distinguish them from
the rest of the GDI/REP family - motif 1 lies in helix 1; motif 2 spans the
C-terminus of helix 2 and helix 3; motif 3 includes strand 5 and the
N-terminus of helix 5; motif 4 spans the C-terminus of helix 7 and the N-
terminus of helix 8; motif 5 encompasses the C-terminus of helix 11 and
helix 12; motif 6 includes strands 10 and 11; motif 7 encompasses strand 14,
helices 16 and 17, and the N-terminus of strand 15; motif 8 spans helix 18
and strand 17; and motif 9 spans strand 18 and helix 20. Two iterations on
OWL30.2 were required to reach convergence, at which point a true set
comprising 23 sequences was identified. Three partial match were also found,
GDIA_MOUSE, HUMGDPDIS and SSZ84059, all of which are fragments that lack one
or more motifs.
An update on SPTR37_9f identified a true set of 23 sequences.
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