2K18

Solution structure of bb' domains of human protein disulfide isomerase

Summary for 2K18

• Entry DOI: 10.2210/pdb2k18/pdb
• Related: 1BJX
• Descriptor: Protein disulfide-isomerase (1 entity in total)
• Functional Keywords: pdi, endoplasmic reticulum, disulfide bonds, protein folding, chaperone, isomerase, membrane, redox-active center
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum lumen: P07237
• Total number of polymer chains: 1
• Total formula weight: 25564.93

Authors

Denisov, A.Y.,Maattanen, P.,Dabrowski, C.,Kozlov, G.,Thomas, D.Y.,Gehring, K. (deposition date: 2008-02-22, release date: 2008-04-29, Last modification date: 2024-05-29)

Primary citation

Denisov, A.Y.,Maattanen, P.,Dabrowski, C.,Kozlov, G.,Thomas, D.Y.,Gehring, K.
Solution structure of the bb' domains of human protein disulfide isomerase.
Febs J., 276:1440-1449, 2009

PubMed Abstract: Protein disulfide isomerase is the most abundant and best studied of the disulfide isomerases that catalyze disulfide bond formation in the endoplasmic reticulum, yet the specifics of how it binds substrate have been elusive. Protein disulfide isomerase is composed of four thioredoxin-like domains (abb'a'). Cross-linking studies with radiolabeled peptides and unfolded proteins have shown that it binds incompletely folded proteins primarily via its third domain, b'. Here, we determined the solution structure of the second and third domains of human protein disulfide isomerase (b and b', respectively) by triple-resonance NMR spectroscopy and molecular modeling. NMR titrations identified a large hydrophobic surface within the b' domain that binds unfolded ribonuclease A and the peptides mastoparan and somatostatin. Protein disulfide isomerase-catalyzed refolding of reduced ribonuclease A in vitro was inhibited by these peptides at concentrations equal to their affinity to the bb' fragment. Our findings provide a structural basis for previous kinetic and cross-linking studies which have shown that protein disulfide isomerase exhibits a saturable, substrate-binding site.

PubMed: 19187238
DOI: 10.1111/j.1742-4658.2009.06884.x

Experimental method

SOLUTION NMR