Stanford Synchrotron Radiation Lightsource An Office of Science User Facility

A) Domain structure of the cIAP1-B3R construct. B) Crystal structure of the monomeric form of cIAP1-B3R.

Healthy cells don't live forever; when the body recognizes they have been damaged or infected, or when they undergo stress, cells naturally undergo "apoptosis," a controlled and regulated cell death.

In the early stages of apoptosis, a family of proteins known as caspases is typically activated; caspases break down cellular components required for normal cellular function. As this happens, the cell shrinks and packs itself into a form that allows its removal from tissue by macrophages. In cancer cells, however, this process is frequently defective, allowing tumor growth to proceed unchecked. 

A team of researchers from Genentech recently studied inhibitors of apoptosis (IAP) proteins, which serve as some of the final "brakes" on apoptosis by inhibiting both caspases and their upstream activators. Through crystallography and SAXS studies conducted at SSRL, the Advanced Light Source, and the Advanced Photon Source, the research team solved the structures of the single and double-molecule forms of a fragment of one IAP, cIAP1-B3R, revealing an unexpected arrangement.  This offers an enhanced understanding of how IAP is activated for degradation, and has significant implications for the development of anti-cancer therapeutics aimed at releasing the brakes on apoptosis.