2IUE
Pactolus I-domain: Functional Switching of the Rossmann Fold
Summary for 2IUE
| Entry DOI | 10.2210/pdb2iue/pdb |
| NMR Information | BMRB: 7313 |
| Descriptor | INTEGRIN BETA-2-LIKE PROTEIN (1 entity in total) |
| Functional Keywords | membrane protein, cd, itc, limbs, midas, admidas, membrane, integrin, titration, cell adhesion, transmembrane |
| Biological source | MUS MUSCULUS (HOUSE MOUSE) |
| Total number of polymer chains | 1 |
| Total formula weight | 23433.66 |
| Authors | Sen, M.,Legge, G.B. (deposition date: 2006-06-02, release date: 2007-06-05, Last modification date: 2024-05-15) |
| Primary citation | Sen, M.,Legge, G.B. Pactolus I-Domain: Functional Switching of the Rossmann Fold. Proteins, 68:626-, 2007 Cited by PubMed 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. PubMed: 17523188DOI: 10.1002/PROT.21458 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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