PDBsum entry 2iue

Membrane protein

PDB id: 2iue

Contents

Protein chain

212 a.a. *

* Residue conservation analysis

PDB id:

2iue

Name:

Membrane protein

Title:

Pactolus i-domain: functional switching of the rossmann fold

Structure:

Integrin beta-2-like protein. Chain: a. Fragment: pactolus i-domain, residues 124-335. Synonym: protein pactolus synonym: adult male bone cdna. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 511693.

NMR struc:

20 models

Authors:

M.Sen,G.B.Legge

Key ref:

M.Sen and G.B.Legge (2007). Pactolus I-domain: functional switching of the Rossmann fold. Proteins, 68, 626-635. PubMed id: 17523188 DOI: 10.1002/prot.21458

Date:

02-Jun-06 Release date: 05-Jun-07

Protein chain

Q3UV74  (ITB2L_MOUSE) -  Integrin beta-2-like protein from Mus musculus

Seq: 738 a.a.

Struc: 212 a.a.

DOI no: 10.1002/prot.21458

Proteins 68:626-635 (2007)

PubMed id: 17523188

Pactolus I-domain: functional switching of the Rossmann fold.

M.Sen, G.B.Legge.

ABSTRACT

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.

Selected figure(s)

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).

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.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2007, 68, 626-635) copyright 2007.

Figures were selected by the author.