During the past two decades, mass spectrometry has become established as the primary method for protein identification from complex mixtures of biological origin. This is largely attributable to the fortunate coincidence of instrumental advances that allow routine analysis of minute amounts (typically femtomoles) of involatile, polar compounds such as peptides in complex mixtures, with the rapid growth in genomic databases that are amenable to searching with mass spectrometry (MS) 1 data. Like many other developing fields in science, the creation of techniques and software tools and the initial generation and interpretation of data have been the domain of experts, people who are cognizant not only of the benefits of the methods but also of their actual and potential weaknesses. Now, as mass spectrometric techniques and proteomic tools become increasingly available and accessible,

We investigate a problem from computational biology: Given a constant size alphabet M with a weight function / : M--> +, find an efficient data structure and query algorithm solving the following problem: For a weight M C + and a string cr over A, decide whether cr contains a substring with weight M (ONE STRING MASS FINDING PROBLEM). If the answer is yes, then we may in addition require a witness, i.e. indices i _ i and ending at position j has weight M. We allow preprocessing of the string, and measure efficiency in two parameters: storage space required for the preprocessed data, and running time of the query algorithm for given M. We are interested in data structures and algorithms requiring subquadratic storage space and sublinear query time, where we measure the input size as the length of the input string. We present two efficient algorithms: LOOKUP solves the problem with O(,) space and (Wg ' loglog,) time; INTERVAL solves the problem for binary alphabets with O0, ) space in O(log,) time. We sketch a third al-gorithm, CLUSTER, which can be adjusted for a space time tradeoff but for which we do not yet have a resource analysis. We introduce a function on weighted strings which is closely related to the analysis of algorithms for the ONE STRING MASS FINDING PROBLEM: The number of different submasses of a weighted string. We present several properties of this function, including upper and lower bounds. Finally, we introduce two more general variants of the problem and sketch how algorithms may be extended for these variants.

Saccharomyces cerevisiae Scc2 binds Scc4 to form an essential complex that loads cohesin onto chromosomes. The prevalence of Scc2 orthologs in eukaryotes emphasizes a conserved role in regulating sister chromatid cohesion, but homologs of Scc4 have not hitherto been identified outside certain fungi. Some metazoan orthologs of Scc2 were initially identified as developmental gene regulators, such as Drosophila Nipped-B, a regulator of cut and Ultrabithorax, and delangin, a protein mutant in Cornelia de Lange syndrome. We show that delangin and Nipped-B bind previously unstudied human and fly orthologs of Caenorhabditis elegans MAU-2, a non-axis-specific guidance factor for migrating cells and axons. PSI-BLAST shows that Scc4 is evolutionarily related to metazoan MAU-2 sequences, with the greatest homology evident in a short N-terminal domain, and protein–protein interaction studies map the site of interaction between delangin and human MAU-2 to the N-terminal regions of both proteins. Short interfering RNA knockdown of human MAU-2 in HeLa cells resulted in precocious sister chromatid separation and in impaired loading of cohesin onto

With the progress of the human genome project, a largescale analysis of proteins within a single experiment, called proteomics, has gained much attention. Mass spectrometry and related techniques have rapidly developed with genome database availability. Using mass spectrometry techniques, one can identify proteins in the database without going through the tedious and time-consuming traditional techniques of HPLC 2 peptide mapping and then Edman degradation, oligonucleotides synthesis, PCR, and gene cloning. Thus, mass spectrometry techniques are gaining popularity as a versatile method for protein identification. Compared with traditional protein sequencing techniques, mass spectrometry analysis of protein is much more sensitive and faster. Now that these techniques are available, the question is, “How we can apply them to biomedical science? ” In this issue, Le Naour et al. (1) apply proteomics-based

1. Electron-microscope tomography of unstained, whole cells 2 2. Cell culture and biomass production 3 3. Purification of protein complexes 4 4. Identification of protein components by mass spectroscopy 11 5. Characterization by single-particle electron microscopy 14 Phylogenetic and functional analysis of GroEL quaternary structure 17

Cytoskeletal dynamics at the Golgi apparatus are regulated in part through a binding interaction between the Golgi-vesicle coat protein, coatomer, and the regulatory GTP-binding protein Cdc42 (Wu,