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PDBsum entry 2iue
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Membrane protein
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PDB id
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2iue
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References listed in PDB file
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Key reference
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Title
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Pactolus I-Domain: functional switching of the rossmann fold.
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Authors
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M.Sen,
G.B.Legge.
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Ref.
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Proteins, 2007,
68,
626-635.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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Murine Pactolus is a neutrophil-specific single chain glycoprotein that plays a
role as an apoptosis marker for macrophages. The extracellular region of the
protein shows strong sequence similarities to integrin beta-subunits. Critical
sequence modifications differentiate its function when compared to the integrin
family. We show experimentally that Pactolus I-domain does not bind divalent
metal ions, indicating that ligand binding is not mediated through a metal
ion-dependent adhesion site (MIDAS). NMR data was used to map secondary
structure and the strand pairing within the beta-sheet to confirm an overall
Rossmann fold topology. Homology modeling enhanced by the NMR data was used to
determine the overall structure, with two key loop insertions/deletions
(insertion 2 and SDL) that distinguish the Pactolus I-domain from the integrin
alpha I-domain and beta I-domains. NMR peak exchange broadening is observed due
to dimerization, correlating to the beta I-domain and beta propeller
heterodimerization region within the integrin headpiece. Two unique N-linked
glycosylation sites (Asn151 and Asn230) within this region disrupt dimerization
and may account for why Pactolus is not found to associate with an
alpha-subunit. These changes in quaternary structure, ligand binding loops,
glycosylation, and metal sites illustrate how evolution has rapidly and
effectively altered key aspects of the integrin beta-subunit to derive a protein
of novel function on an existing protein scaffold.
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Figure 4.
Figure 4. Parallel and antiparallel  -structure
in the Pactolus I-domain, with observed NOEs indicated by a wavy
line, and the predicted hydrogen bonds from solvent exchange
protected amides is shown as a dashed line. Figure was generated
using ChemDraw Ultra10.0 (CambridgeSoft Corporation).
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Figure 6.
Figure 6. Pactolus I-domain forms a dimer in the solution a)
Ribbon diagram of the lowest energy structure with the three
unassigned regions (Leu180-Ile195, Asn215-Ala220, and
Ser245-Leu261) highlighted and labeled in red and the predicted
N-glycosylation sites in green as depicted with the program
MOLMOL.[40]b) The two potential N-linked glycosylation residues
of Pactolus I-domain (Asn151 and Asn230) may disrupt the
formation of an integrin headpiece.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2007,
68,
626-635)
copyright 2007.
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