Structural and Functional Proteomics-Protemics-Lecture Slides, Slides of Proteomics

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STRUCTURAL AND

PROTEOMICSFUNCTIONAL

What is structural

proteomics/genomics?

of proteinsHigh-throughput determination of the 3D structure

• Direct determination - X-ray crystallography andstructure of every protein.Goal: to be able to determine or predict the nuclear magentic resonance (NMR).
• Prediction
• Ab initio• Threading/Fold recognition• Comparative modeling -

An example

prokaryotes, mitochondria, and chloroplasts.FtsZ - protein required for cell division in

division.important for intracellular trafficking and cellTubulin - structural component of microtubules -

proteins by sequence analysis.and would not be identified as homologousFtsZ and Tubulin have limited sequence similarity

Burns, R., Nature

(^) 391 :121-

Picture from E. Nogales

sequence levelsimilarity at the amino acidFtsZ and tubulin have little

Current state of structural

proteomics

• Only 1600 non-redundant structuresAs of Feb. 2002 - 16,500 structures

• Of the 2300 structures deposited in 2000, only 11%16,000 novel sequences needed for 90% coverage.To identify all possible folds - predicted another contained previously unidentified folds.

future proteins.directly to be able to computationally model allOverall goal - directly solve enough structures

Protein domains - structure

• “clearly recognizable portion of a protein
• Doesn’t have to be the same as the domains wethat folds into a defined structure” have been investigating with CDD.
• RbsB proteins as an example.

http://www.expasy.org/swissmod/course/text/chapter1.htmImages from http://www-structure.llnl.gov/Xray/tutorial/protein_structure.htm

Folds/motifs

• How these secondary structure elements
• Helix-turn-helixcome together to form structure.
• Determining the structure of nearly all folds

is the goal of structural biology

Image from http://www-structure.llnl.gov/Xray/101index.html

Schmid, M. Trends in Microbiolgy,

(^) 10 :s27-s31.

Nuclear Magnetic Resonance

Spectroscopy (NMR)

• Can perform in solution.
• No need for crystallization
• Can only analyze proteins that are <300aa.
• Can’t analyze multi-subunit complexes– Many proteins are much larger.
• Proteins must be stable.

Structure modeling

• Modeling the structure of a protein that has a highComparative modeling structuredegree of sequence identity with a protein of known
• Must be >30% identity to have reliable structure

• Uses known fold structures to predict folds in primaryThreading/fold recognition sequence.

• Usually not as robust, computationally intensive– Predicting structure from primary sequence dataAb initio

Structure of the ribosome

• Ribosome - made up of 2 major RNA

molecules and over 50 proteins.

• Structure of the 70S ribosome solved by

30S and 50S subunitscombining several models of the individual

• Ramakrishnan V. (2002) Cell. 108(4):557-