Structural genomics target selection for the New York consortium on membrane protein structure

Area of Science:

• Structural biology
• Biochemistry
• Genomics

Background:

• Integral membrane proteins play crucial roles in cellular functions but are challenging to study structurally.
• The Protein Structure Initiative (PSI) aims to determine novel protein structures, including membrane proteins.
• The New York Consortium on Membrane Protein Structure (NYCOMPS) focuses on high-throughput determination of integral membrane protein structures.

Purpose of the Study:

• To describe the target selection protocol used by NYCOMPS for identifying novel integral membrane protein structures.
• To apply structural genomics approaches for efficient and effective target selection.
• To expand the structural coverage of membrane protein space.

Main Methods:

• Extraction and filtering of annotated proteins from 96 fully sequenced prokaryotic genomes.
• Definition of 'valid targets' based on criteria including predicted transmembrane helices and lack of disordered regions.
• Selection of proteins for the experimental pipeline using a 'seed' protein approach with sequence similarity requirements in the transmembrane region.

Main Results:

• Over 6,000 targets have been selected and are currently in the experimental pipeline as of December 2008.
• The protocol identifies targets with at least two predicted transmembrane helices and no long disordered regions.
• A significant portion of selected targets show no significant sequence similarity in their transmembrane regions to known structures, indicating novelty.

Conclusions:

• The described target selection protocol effectively identifies novel integral membrane protein candidates for structural determination.
• This approach, utilizing structural genomics and a seed-based strategy, is crucial for expanding the structural database of membrane proteins.
• The NYCOMPS target list is expected to significantly impact the overall structural coverage of membrane protein families.