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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Reca Dimers Serve As A Functional Unit For Assembly Of Active Nucleoprotein Filaments, Anthony Forget, Michelle Kudron, Dharia Mcgrew, Melissa Calmann, Celia Schiffer, Kendall Knight
Reca Dimers Serve As A Functional Unit For Assembly Of Active Nucleoprotein Filaments, Anthony Forget, Michelle Kudron, Dharia Mcgrew, Melissa Calmann, Celia Schiffer, Kendall Knight
Celia A. Schiffer
All RecA-like recombinase enzymes catalyze DNA strand exchange as elongated filaments on DNA. Despite numerous biochemical and structural studies of RecA and the related Rad51 and RadA proteins, the unit oligomer(s) responsible for nucleoprotein filament assembly and coordinated filament activity remains undefined. We have created a RecA fused dimer protein and show that it maintains in vivo DNA repair and LexA co-protease activities, as well as in vitro ATPase and DNA strand exchange activities. Our results support the idea that dimeric RecA is an important functional unit both for assembly of nucleoprotein filaments and for their coordinated activity during the …
Insights Into Interferon Regulatory Factor Activation From The Crystal Structure Of Dimeric Irf5, Weijun Chen, Suvana Lam, Hema Srinath, Zhaozhao Jiang, John Correia, Celia Schiffer, Katherine Fitzgerald, Kai Lin, William Royer
Insights Into Interferon Regulatory Factor Activation From The Crystal Structure Of Dimeric Irf5, Weijun Chen, Suvana Lam, Hema Srinath, Zhaozhao Jiang, John Correia, Celia Schiffer, Katherine Fitzgerald, Kai Lin, William Royer
Celia A. Schiffer
Interferon regulatory factors (IRFs) are essential in the innate immune response and other physiological processes. Activation of these proteins in the cytoplasm is triggered by phosphorylation of serine and threonine residues in a C-terminal autoinhibitory region, which stimulates dimerization, transport into the nucleus, assembly with the coactivator CBP/p300 and initiation of transcription. The crystal structure of the transactivation domain of pseudophosphorylated human IRF5 strikingly reveals a dimer in which the bulk of intersubunit interactions involve a highly extended C-terminal region. The corresponding region has previously been shown to block CBP/p300 binding to unphosphorylated IRF3. Mutation of key interface residues supports …
How Does A Symmetric Dimer Recognize An Asymmetric Substrate? A Substrate Complex Of Hiv-1 Protease, Moses Prabu-Jeyabalan, Ellen Nalivaika, Celia Schiffer
How Does A Symmetric Dimer Recognize An Asymmetric Substrate? A Substrate Complex Of Hiv-1 Protease, Moses Prabu-Jeyabalan, Ellen Nalivaika, Celia Schiffer
Celia A. Schiffer
The crystal structure of an actual HIV-1 protease-substrate complex is presented at 2.0 A resolution (R-value of 19.7 % (R(free) 23.3 %)) between an inactive variant (D25N) of HIV-1 protease and a long substrate peptide, Lys-Ala-Arg-Val-Leu-Ala-Glu-Ala-Met-Ser, which covers a full binding epitope of capsid(CA)-p2, cleavage site. The substrate peptide is asymmetric in both size and charge distribution. To accommodate this asymmetry the two protease monomers adopt different conformations burying a total of 1038 A(2) of surface area at the protease-substrate interface. The specificity for the CA-p2 substrate peptide is mainly hydrophobic, as most of the hydrogen bonds are made with …
Structure Of A Phage Display-Derived Variant Of Human Growth Hormone Complexed To Two Copies Of The Extracellular Domain Of Its Receptor: Evidence For Strong Structural Coupling Between Receptor Binding Sites, Celia Schiffer, Mark Ultsch, Scott Walsh, William Somers, Abraham De Vos, Anthony Kossiakoff
Structure Of A Phage Display-Derived Variant Of Human Growth Hormone Complexed To Two Copies Of The Extracellular Domain Of Its Receptor: Evidence For Strong Structural Coupling Between Receptor Binding Sites, Celia Schiffer, Mark Ultsch, Scott Walsh, William Somers, Abraham De Vos, Anthony Kossiakoff
Celia A. Schiffer
The structure of the ternary complex between the phage display- optimized, high-affinity Site 1 variant of human growth hormone (hGH) and two copies of the extracellular domain (ECD) of the hGH receptor (hGHR) has been determined at 2.6 A resolution. There are widespread and significant structural differences compared to the wild-type ternary hGH hGHR complex. The hGH variant (hGH(v)) contains 15 Site 1 mutations and binds>10(2) tighter to the hGHR ECD (hGH(R1)) at Site 1. It is biologically active and specific to hGHR. The hGH(v) Site 1 interface is somewhat smaller and 20% more hydrophobic compared to the wild-type …