Fitting a PCB into the lung milieu.

High exposures to polychlorinated biphenyls (PCBs), oils that serve as electrical insulators, can cause serious damage to the lungs. Swedish researchers have now used magnetic resonance imaging (MRI) to probe why certain PCBs collect in the lungs once they have been altered slightly by the body. The resulting structural portrait of one such metabolite and its usual intimate companion, a protein secreted by the lung, now answer the important question of how the two could couple.

The lung's uteroglobin protein seemed to have no opening through which a PCB or a metabolite could enter to dock at internal binding sites, explains Torlief Haerd of the Karolinska Institute in Huddinge. But in the November Nature Structural Biology, his team shows that in some instances, disulfide bonds in the protein split open ike a drawbridge. "Presumably, that's how the [PCB] gets in," he says. When the protein returns to its normal state, the bridge closes, locking in the PCB so it can travel wherever the uteroglobin goes.

"This is very unusual," Haerd observes. "Normally,disulfide bonds stabilize the whole protein." He notes that the PCB also fits the interior pocket of the protein perfectly. He says that one working hypothesis posits that these PCBs may exert their toxic effects "by fitting too perfectly, by binding too tightly" and in so doing "exaggerate or block the normal function of the protein." Indeed, notes coauthor Johan Lund, the only natural compound known to bind to uteroglobin is the hormone progesterone. These PCBs "bind with a 1,000-fold higher affinity."