Results tagged “cover” 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.

Taherbhoy AM, Tait SW, Kaiser SE, Williams AH, Deng A, Nourse A, Hammel M, Kurinov I, Rock CO, Green DR, Schulman BA. “Atg8 transfer from atg7 to atg3: a distinctive e1-e2 architecture and mechanism in the autophagy pathway.” Mol Cell 2011 Nov.;44(3):451-461.
Rambo_RNA.gifCover Illustration from the September 2009 issue of RNA: Crystal structure of the lysine riboswitch bound to lysine (Protein Data Bank code: 3d0u) Image details show RNA: ribbon; lysine: space-filling representation, red; iridium hexamine ions: space-filling representation, blue.

Riboswitches are metabolite-sensitive elements found in mRNAs that control gene expression through a regulatory secondary structural switch. Along with regulation of lysine biosynthetic genes, mutations within the lysine-responsive riboswitch (L-box) play a role in the acquisition of resistance to antimicrobial lysine analogs. To understand the structural basis for lysine binding, we have determined the 2.8 angstroms resolution crystal structure of lysine bound to the Thermotoga maritima asd lysine riboswitch ligand-binding domain. The structure reveals a complex architecture scaffolding a binding pocket completely enveloping lysine. Mutations conferring antimicrobial resistance cluster around this site as well as highly conserved long range interactions, indicating that they disrupt lysine binding or proper folding of the RNA. Comparison of the free and bound forms by x-ray crystallography, small angle x-ray scattering, and chemical probing reveals almost identical structures, indicating that lysine induces only limited and local conformational changes upon binding.

Garst AD, Héroux A, Rambo RP, Batey RT. "Crystal structure of the lysine riboswitch regulatory mRNA element." J Biol Chem. 2008 Aug 15;283(33):22347-51. Epub 2008 Jul 1.
link out

ALS Ring Status

loading ...



Powered by Movable Type 5.2.13

January 2019

Sun Mon Tue Wed Thu Fri Sat
    1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18 19
20 21 22 23 24 25 26
27 28 29 30 31