Structural Genomics of Membrane Proteins

P01 GM54160-02 (PI Engelman)
7/1/99 - 6/30/04
Structural Genomics of Membrane Proteins
Role: subproject PI

This is a subproject of a program project entitled "Structural Motifs in Membrane Proteins". The subproject focuses on large-scale genome surveys of membrane proteins and their sequence motifs.

[Aim 1]

Our first aim is to apply methods to inventory all membrane proteins and membrane-associated proteins in recently sequenced genomes.

[Aim 2]

Our second aim is to look at protein-protein interactions among helical membrane proteins from a database perspective. We wanted to put the TM-helix oligomerization motifs found in the genetic screens by the Beckwith and Engelman groups (e.g. GXXXG) into a context by comparing them to the helix-helix interfaces in the database of known structures -- both of the many soluble proteins and the few TM ones. In this context we were particularly keen to focus on protein flexibility and to analyze whole-genome information on protein-protein interactions.

[Aim 3]

Our final aim was to integrate into a comprehensive database the information on the occurrence and interaction of membrane proteins generated in the first two aims with further information, e.g. related to expression.
Related material:
Year 1 report [ doc ][ html ]
Year 2 report [ doc ][ html ]
Year 3 report [ doc ][ html ]
Year 4 report [ doc ][ html ]

Overall report [ doc ][ html ]

Articles funded by this grant:
Use of thioredoxin as a reporter to identify a subset of Escherichia coli signal sequences that promote signal recognition particle-dependent translocation.
D Huber, D Boyd, Y Xia, MH Olma, M Gerstein, J Beckwith (2005). J Bacteriol 187: 2983-91.

Sequence variation in G-protein-coupled receptors: analysis of single nucleotide polymorphisms.
S Balasubramanian, Y Xia, E Freinkman, M Gerstein (2005). Nucleic Acids Res 33: 1710-21.

Calculation of standard atomic volumes for RNA and comparison with proteins: RNA is packed more tightly.
NR Voss, M Gerstein (2005). J Mol Biol 346: 477-92.

Computational analysis of membrane proteins: genomic occurrence, structure prediction and helix interactions.
U Lehnert, Y Xia, TE Royce, CS Goh, Y Liu, A Senes, H Yu, ZL Zhang, DM Engelman, M Gerstein (2004). Q Rev Biophys 37: 121-46.

Analyzing cellular biochemistry in terms of molecular networks.
Y Xia, H Yu, R Jansen, M Seringhaus, S Baxter, D Greenbaum, H Zhao, M Gerstein (2004). Annu Rev Biochem 73: 1051-87.

Selection and characterization of small random transmembrane proteins that bind and activate the platelet-derived growth factor beta receptor.
LL Freeman-Cook, AM Dixon, JB Frank, Y Xia, L Ely, M Gerstein, DM Engelman, D DiMaio (2004). J Mol Biol 338: 907-20.

Transmembrane protein domains rarely use covalent domain recombination as an evolutionary mechanism.
Y Liu, M Gerstein, DM Engelman (2004). Proc Natl Acad Sci U S A 101: 3495-7.

TopNet: a tool for comparing biological sub-networks, correlating protein properties with topological statistics.
H Yu, X Zhu, D Greenbaum, J Karro, M Gerstein (2004). Nucleic Acids Res 32: 328-37.

The human genome has 49 cytochrome c pseudogenes, including a relic of a primordial gene that still functions in mouse.
Z Zhang, M Gerstein (2003). Gene 312: 61-72.

A method to assess compositional bias in biological sequences and its application to prion-like glutamine/asparagine-rich domains in eukaryotic proteomes.
PM Harrison, M Gerstein (2003). Genome Biol 4: R40.

Calculations of protein volumes: sensitivity analysis and parameter database.
J Tsai, M Gerstein (2002). Bioinformatics 18: 985-95.

Subcellular localization of the yeast proteome.
A Kumar, S Agarwal, JA Heyman, S Matson, M Heidtman, S Piccirillo, L Umansky, A Drawid, R Jansen, Y Liu, KH Cheung, P Miller, M Gerstein, GS Roeder, M Snyder (2002). Genes Dev 16: 707-19.

Thermostability of membrane protein helix-helix interaction elucidated by statistical analysis.
D Schneider, Y Liu, M Gerstein, DM Engelman (2002). FEBS Lett 532: 231-6.

Systematic learning of gene functional classes from DNA array expression data by using multilayer perceptrons.
A Mateos, J Dopazo, R Jansen, Y Tu, M Gerstein, G Stolovitzky (2002). Genome Res 12: 1703-15.

Digging deep for ancient relics: a survey of protein motifs in the intergenic sequences of four eukaryotic genomes.
ZL Zhang, PM Harrison, M Gerstein (2002). J Mol Biol 323: 811-22.

GeneCensus: genome comparisons in terms of metabolic pathway activity and protein family sharing.
J Lin, J Qian, D Greenbaum, P Bertone, R Das, N Echols, A Senes, B Stenger, M Gerstein (2002). Nucleic Acids Res 30: 4574-82.

Genomic analysis of membrane protein families: abundance and conserved motifs.
Y Liu, DM Engelman, M Gerstein (2002). Genome Biol 3: research0054.

Protein Geometry: Distances, Areas, and Volumes
M Gerstein, F M Richards (2001). International Tables for Crystallography (Volume F, Chapter 22.1.1, pages 531-539; M Rossmann & E Arnold, editors; Dordrecht: Kluwer)

Digging for dead genes: an analysis of the characteristics of the pseudogene population in the Caenorhabditis elegans genome.
PM Harrison, N Echols, MB Gerstein (2001). Nucleic Acids Res 29: 818-30.

PartsList: a web-based system for dynamically ranking protein folds based on disparate attributes, including whole-genome expression and interaction information.
J Qian, B Stenger, CA Wilson, J Lin, R Jansen, SA Teichmann, J Park, WG Krebs, H Yu, V Alexandrov, N Echols, M Gerstein (2001). Nucleic Acids Res 29: 1750-64.

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