User:Wayne Decatur/UNH BCHEM833 Structural Proteomics Introductory Lecture Fall 2012

From Proteopedia

A Common Starting Point

• IProtein App review placing topic in a broader context to show relevance and introduce concepts to be covered today
• Table of Contents from the May Issue of Science to focus on two Perspectives that further place topic in context, showing broad relevance, the related fields evolving, and give us an example we can keep using and provide one of may paths for those interested to explore further if they wish. (No particular reason for these as examples, other than the block of papers caught my eye.) Specifically the two Perspectives of interest:
  • Evans P. Biochemistry. Resolving some old problems in protein crystallography. Science. 2012 May 25;336(6084):986-7. PubMed PMID: 22628641.^[1]
    • Perspective on:
      • Karplus PA, Diederichs K. Linking crystallographic model and data quality. Science. 2012 May 25;336(6084):1030-3. PubMed PMID: 22628654^[2]
      • Liu Q, Dahmane T, Zhang Z, Assur Z, Brasch J, Shapiro L, Mancia F, Hendrickson WA. Structures from anomalous diffraction of native biological macromolecules. Science. 2012 May 25;336(6084):1033-7. PubMed PMID: 22628655.^[3]
  • Kaya E, Doudna JA. Biochemistry. Guided tour to the heart of RISC. Science. 2012 May 25;336(6084):985-6. PubMed PMID: 22628640.^[4]
    • Perspective on: Schirle NT, MacRae IJ. The crystal structure of human Argonaute2. Science. 2012 May 25;336(6084):1037-40. Epub 2012 Apr 26. PubMed PMID: 22539551 paper on Crystal Structure of Human Argonaute2 in complex with guide RNA^[5], which features 4ei1.

Key Resources

• Proteopedia
• Protein Data Bank
• PDBsum
• Protein Structure Initiative:Biology program
• The International Structural Genomics Consortium
• ConSurf-DB (The ConSurf Database) and The ConSurf Server
• Syllabus for Eric Martz's 2-day workshop on Macromolecular Visualization
• The "Top 5" 3D Molecular Visualization Technologies for non-structural biologists
• POLYVIEW-3D - FAST ROUTE- liberates you from needing to learn a software package to make publication quality images. Just fill out forms. See also Web servers for convenient generation of publication-quality figures for molecular views.

Discussed Items

• Methods for Determining Atomic Structures, hosted at the PDB
  • X-ray crystallography
    • Fraction and number of structures
    • Resolution and hydrogens.
  • NMR Ensembles of Models
• Figure 1 illustrates strategies for solving structures of GPCRs, from TiBS article by Tate^[6].
• PDB poster and quick reference guide
• PDB file format in Proteopedia. Plus hetero atoms/ligands.
• Article entitled Consortium solves its 1,000th protein structure^[7] - the international Structural Genomics Consortium celebrates its focus on expensive but exciting targets. (Covers some of controversy about such approaches and mentions US-based Protein Structure Initiative:Biology program).
  • 1,000 structures and more from the MCSG. 2011. BMC Struct Biol. Jan 10;11:2. ^[8] "We show that the MCSG has met the stated goals of the PSI and use online resources and readily available function prediction methods to provide functional annotations for more than 90% of the MCSG structures. The structure-to-function prediction method ProFunc provides likely functions for many of the MCSG structures that cannot be annotated by sequence-based methods."
  • The Proteome Folding Project: Proteome-scale prediction of structure and function. 2011. BMC Struct Biol. Jan 10;11:2. ^[9].
• Secondary structure displayed under the Contents link at the PDBsum or the Sequence tab at the PDB.
• Molecular Visualization and Viewers
• For analysis of buried surface areas in structural complexes:
  • I suggest PDBsum reports. See Interface analysis servers. Example: 3sn6 Prot-prot interface report or 1aoi Prot-prot interface report
  • Calculate in PyMol --> http://www.pymolwiki.org/index.php/Get_Area
• Compare your protein to others, see Acknowledgments therein for references^[10]. Also see the '3D similarity' tab for each structure in the PDB].
• Introduction to Evolutionary Conservation and How to see conserved regions. Enolase is used for viewing structural conservation and illustrating ligands.
• Caveats:
  
  • Asymmetric Unit unit vs. the biological assembly or biological unit.
    • Also, good information comes up with the PQS button in Firstglance in Jmol.
    • Also see Looking at Structures: Introduction to Biological Assemblies and the PDB Archive.
    • Example is bar-headed goose hemoglobin.
  • Considering Biological relevance, which can involve evaluating Crystal contacts
  • Gaps and disorder
    • see Missing Residues and Disorder on the Temperature value page
    • Also see Intrinsically Disordered Protein
• 10th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction

Molecular Visualization and Viewers

(Generally, arranged in order of increasing complexity:)

• Proteopedia
• Firstglance in Jmol
• Jena3D Viewer
• Polyview-3D = fancy PyMol views and animations made super easy via a web server with forms.
• Jmol for download
• DeepView - Swiss-PdbViewer
• UCSF Chimera
• PyMol
• ChimeraX

Example Structures Used or Discussed in Class

• Crystal Structure of Human Argonaute2 in complex with guide RNA
• A human G protein-coupled receptor (GPCR), the beta-2 adrenergic receptor, in complex with a G protein featured on the Proteopedia page on G protein-coupled receptors (GPCRs). This structure was in the news recently because of the Nobel Prizes being awarded. The specific structure featured is 3sn6, as described in 2011 ^[11][12]. A Perspective on the structure is in the same issue^[13].
• The Nucleosome
• Bar-headed goose hemoglobin is used for discussing biological unit.
• Enolase is used for viewing structural conservation and illustrating ligands.
• Crystal Structure of a Catalytically Active Substrate-Bound Box C/D RNP From Sulfolobus Solfataricus
• The Ribosome

Notes and References

1. ↑ Evans P. Biochemistry. Resolving some old problems in protein crystallography. Science. 2012 May 25;336(6084):986-7. PMID:22628641 doi:10.1126/science.1222162
2. ↑ Karplus PA, Diederichs K. Linking crystallographic model and data quality. Science. 2012 May 25;336(6084):1030-3. PMID:22628654 doi:10.1126/science.1218231
3. ↑ Liu Q, Dahmane T, Zhang Z, Assur Z, Brasch J, Shapiro L, Mancia F, Hendrickson WA. Structures from anomalous diffraction of native biological macromolecules. Science. 2012 May 25;336(6084):1033-7. PMID:22628655 doi:10.1126/science.1218753
4. ↑ Kaya E, Doudna JA. Biochemistry. Guided tour to the heart of RISC. Science. 2012 May 25;336(6084):985-6. PMID:22628640 doi:10.1126/science.1223549
5. ↑ Schirle NT, Macrae IJ. The Crystal Structure of Human Argonaute2. Science. 2012 Apr 26. PMID:22539551 doi:10.1126/science.1221551
6. ↑ Tate CG. A crystal clear solution for determining G-protein-coupled receptor structures. Trends Biochem Sci. 2012 Sep;37(9):343-52. Epub 2012 Jul 10. PMID:22784935 doi:10.1016/j.tibs.2012.06.003
7. ↑ Ledford, H. Consortium solves its 1,000th protein structure. Published online 30 September 2010. Nature doi:10.1038/news.2010.500
8. ↑ Lee D, de Beer TA, Laskowski RA, Thornton JM, Orengo CA. 1,000 structures and more from the MCSG. BMC Struct Biol. 2011 Jan 10;11:2. PMID:21219649 doi:10.1186/1472-6807-11-2
9. ↑ Drew K, Winters P, Butterfoss GL, Berstis V, Uplinger K, Armstrong J, Riffle M, Schweighofer E, Bovermann B, Goodlett DR, Davis TN, Shasha D, Malmstrom L, Bonneau R. The Proteome Folding Project: proteome-scale prediction of structure and function. Genome Res. 2011 Nov;21(11):1981-94. Epub 2011 Aug 8. PMID:21824995 doi:10.1101/gr.121475.111
10. ↑ I don't see SCOP (Structural Clasification of Proteins) listed there but is listed in analysis towards top of the page.
11. ↑ Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah ST, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK. Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature. 2011 Jul 19;477(7366):549-55. doi: 10.1038/nature10361. PMID:21772288 doi:10.1038/nature10361
12. ↑ Chung KY, Rasmussen SG, Liu T, Li S, DeVree BT, Chae PS, Calinski D, Kobilka BK, Woods VL Jr, Sunahara RK. Conformational changes in the G protein Gs induced by the beta2 adrenergic receptor. Nature. 2011 Sep 28;477(7366):611-5. doi: 10.1038/nature10488. PMID:21956331 doi:10.1038/nature10488
13. ↑ Schwartz TW, Sakmar TP. Structural biology: snapshot of a signalling complex. Nature. 2011 Sep 28;477(7366):540-1. doi: 10.1038/477540a. PMID:21956322 doi:10.1038/477540a

Additional Resources that may be helpful on interesting

• Page from a 2011 Workshop given by Wayne Decatur that has a wealth of information for further exploring
• Orientations of Proteins in Membranes (OPM) database from the University of Michigan (Ann Arbor, Michigan, USA), and knowing the spatial arrangement of protein with respect to the hydrocarbon core of the lipid bilayer and other details of topology
• POLYVIEW-3D makes publication-quality images and animations of structures via a form you fill out
• Eric Martz's future page for a class an introductory class he is teaching in 2013
• Students at UMASS in classes associated with Chemistry-Biology Interface program design presentations for showing on the Molecular Playground. An example is Relenza for the Molecular Playground.
• Molecular modeling and visualization software

Workshop Session for November 8th class

• UNH BCHEM833 Structural Analysis Workshop Session Fall 2012