Group:USC-LCHS
From Proteopedia
The Rohs Lab at USC and Protein-DNA Institute at La Cañada High School
Welcome, students, fellow researchers and educators! Welcome to your home page for the joint structural biology initiative between the Rohs Lab at the University of Southern California (USC) and the Protein-DNA Institute at La Cañada High School (LCHS), hosted on the Proteopedia web resource. The goal of this website is to provide a cyber-infrastructure for the use of graphic visualization tools in integrated educational and research activities focused at structural aspects of proteins and nucleic acids. You will notice that this is not a regular webpage. If you scroll down a bit, you will find that there are interactive 3D structures of protein-DNA complexes on this page. You can even trigger animations by clicking on green hyperlinks in the text when you find them. These green hyperlinks will change the orientation and representation of the 3D structure in order to illustrate a point made in the related scientific publication. The best part is that it is easy to create your own page with an interactive 3D structure and green links, and that is what you will be doing to present your findings! Feel free to also explore other pages in Proteopedia that are not related to USC-LCHS. Proteopedia is a collaborative 3D encyclopedia of proteins and other biomolecules, and you will find many interesting molecules described in interactive detail.
Example: Readout of DNA minor groove shape is the molecular basis for Hox specificity
The recognition of specific DNA-binding sites by transcription factors is a critical yet poorly understood step in the control of gene expression. Members of the Hox family of transcription factors bind DNA by making nearly identical major groove contacts via the recognition helices of their homeodomains. In vivo specificity, however, often depends on extended and unstructured regions that link Hox homeodomains to a DNA-bound cofactor, Extradenticle (Exd). Using a combination of structure determination, computational analysis, and in vitro and in vivo assays, we show that Hox proteins recognize specific Hox-Exd binding sites via residues located in these extended regions that insert into the minor groove but only when presented with the correct DNA sequence. Our results suggest that these residues, which are conserved in a paralog-specific manner, confer specificity by recognizing a sequence-dependent DNA structure instead of directly reading a specific DNA sequence. Functional specificity of a Hox protein mediated by the recognition of minor groove structure., Joshi R, Passner JM, Rohs R, Jain R, Sosinsky A, Crickmore MA, Jacob V, Aggarwal AK, Honig B, Mann RS, Cell. 2007 Nov 2;131(3):530-43. PMID:17981120 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. |
| ||||||||||
Example: Hoogsteen base pairs modulate shape of p53-DNA binding site
| p53 binds as a tetramer to DNA targets consisting of two decameric half-sites separated by a variable spacer. Here we present high-resolution crystal structures of complexes between p53 core-domain tetramers and DNA targets consisting of contiguous half-sites. In contrast to previously reported p53-DNA complexes that show standard Watson-Crick base pairs, the newly reported structures show noncanonical Hoogsteen base-pairing geometry at the central A-T doublet of each half-site. Structural and computational analyses show that the Hoogsteen geometry distinctly modulates the B-DNA helix in terms of local shape and electrostatic potential, which, together with the contiguous DNA configuration, results in enhanced protein-DNA and protein-protein interactions compared to noncontiguous half-sites. Our results suggest a mechanism relating spacer length to protein-DNA binding affinity. Our findings also expand the current understanding of protein-DNA recognition and establish the structural and chemical properties of Hoogsteen base pairs as the basis for a novel mode of sequence readout. Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs., Kitayner M, Rozenberg H, Rohs R, Suad O, Rabinovich D, Honig B, Shakked Z, Nat Struct Mol Biol. 2010 Apr;17(4):423-9. Epub 2010 Apr 4. PMID:20364130 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. | ||||||||||
