Results tagged “highlight” from The SIBYLS Beamline
SAXS data collected at the SIBYLS beamline was used in conjunction with high resolution crystals structures to discern details of the unique interaction mode of of these key players in the autophagy pathway.
Atg7 is a noncanonical, homodimeric E1 enzyme that interacts with the noncanonical E2 enzyme, Atg3, to mediate conjugation of the ubiquitin-like protein (UBL) Atg8 during autophagy. Here we report that the unique N-terminal domain of Atg7 (Atg7NTD) recruits a unique “flexible region” from Atg3 (Atg3FR). The structure of an Atg7NTD-Atg3FR complex reveals hydrophobic residues from Atg3 engaging a conserved groove in Atg7, important for Atg8 conjugation. We also report the structure of the homodimeric Atg7 C-terminal domain, which is homologous to canonical E1s and bacterial antecedents. The structures, SAXS, and crosslinking data allow modeling of a full-length, dimeric (Atg7∼Atg8-Atg3)2 complex. The model and biochemical data provide a rationale for Atg7 dimerization: Atg8 is transferred in trans from the catalytic cysteine of one Atg7 protomer to Atg3 bound to the N-terminal domain of the opposite Atg7 protomer within the homodimer. The studies reveal a distinctive E1∼UBL-E2 architecture for enzymes mediating autophagy.


As recently reported in the ALSNews:
“The veil has finally been lifted on an enzyme that is critical to the process of DNA transcription and replication and is a prime target of antibacterial and anticancer drugs. Researchers at Berkeley Lab and the University of California, Berkeley, have produced the first three-dimensional structural images of a DNA-bound type II topoisomerase (topo II) that is responsible for untangling coiled strands of the chromosome during cell division. Preventing topo II from disentangling a cell’s DNA is fatal to the cell, which is why drugs that target topo II serve as agents against bacterial infections and some forms of cancer. This first ever structural image of topo II should help in the development of future antibacterial and anticancer drugs that are even more effective and carry fewer potential side effects.”
The original publication in Nature can be found here: K.C. Dong and J.M. Berger, “Structural basis for Gate-DNA recognition and bending by type IIA topoisomerases,” Nature 250, 1201 (2007).