Lecture_13-2011 - Structural proteomics Nanoarchaeum...

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Structural proteomics
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Nanoarchaeum equitans - archaea Hyperthermophile Diverged early in evolution from other archaea New kingdom of archaea? Obligate symbiont with Ignicoccus One of the smallest completely sequenced genome <500kB Genome reduction observed in symbionts Is N. equitans a “primitive” archaea or is the genome undergoing reductive evolution?
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N. equitans lacks genes necessary for many aspects of central metabolism. Can’t make lipids, vitamins, amino acids, etc. Parasite, not symbiont? First archaea. Genome is quite compact. 95% of genome codes for genes. 552. Not primitive. Has complete set of information pathway and cell cycle genes found in archaea. No longer undergoing reductive evolution. Normally would find pseudogenes - not found.
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What is structural proteomics/genomics? High-throughput determination of the 3D structure of proteins Goal: to be able to determine or predict the structure of every protein. Direct determination - X-ray crystallography and nuclear magentic resonance (NMR). Prediction Comparative modeling Threading/Fold recognition Ab initio
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Why structural proteomics? To study proteins in their active conformation. Study protein:drug interactions Protein engineering Proteins that show little or no similarity at the primary sequence level can have strikingly similar structures.
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An example FtsZ - protein required for cell division in prokaryotes, mitochondria, and chloroplasts. Tubulin - structural component of microtubules - important for intracellular trafficking and cell division. FtsZ and Tubulin have limited sequence similarity and would not be identified as homologous proteins by sequence analysis.
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Burns, R., Nature 391 :121-123 Picture from E. Nogales FtsZ and tubulin have little similarity at the amino acid sequence level
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Are FtsZ and tubulin homologous? Yes! Proteins that have conserved
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Lecture_13-2011 - Structural proteomics Nanoarchaeum...

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