In This Issue

327 Amyloidogenic sequences in native protein structures

Susan Tzotzos and Andrew J. Doig

Numerous short peptides have been shown to form β-sheet amyloid aggregates in vitro. Proteins that contain such sequences are likely to be problematic for a cell, due to their potential to aggregate into toxic structures. In this report, the authors found that proteins have evolved at the molecular level to deal with these potentially lethal sequences using two mechanisms: Firstly, amyloidogenic sequences are often found within helices, despite their inherent preference to form β structure, presumably since in order to form amyloid they will have to unfold and refold into β strands. Secondly, if amyloidogenic sequences are found in β structure, they are buried.

349 De novo structure generation using chemical shifts for proteins with high-sequence identity but different folds

Yang Shen, Philip N. Bryan, Yanan He, John Orban, David Baker, and Ad Bax

Different folds for proteins with high-sequence identity (>30%) are rare, but such cases may provide insight into the evolution of the wide array of protein folds found in nature. Bryan, Orban, and co-workers started from two domains of protein G with little sequence identity and different folds — a three-helical bundle (GA) and an αβ-fold (GB) — to generate pairs of proteins with sequence identities of up to 98% while retaining their initial folds. Structure prediction for the native sequences (GA and GB) is straightforward, but becomes increasingly challenging when the sequences of the different folds converge. However, when chemical shift information is included in the structure prediction process by using the recently introduced Chemical-Shift-Rosetta program, convergence to the experimentally determined structures is excellent. Remarkably, this remains the case when only backbone amide and Hα chemical shifts are used as input for CS-Rosetta.

242 Versatile modes of peptide recognition by the ClpX N domain mediate alternative adaptor-binding specificities in different bacterial species

Tahmeena Chowdhury, Peter Chien, Shamsah Ebrahim, Robert T. Sauer, and Tania A. Baker

AAA+ proteases, including ClpXP, control the proteome by degrading stress-response, regulatory, and damaged proteins. ClpX has an N-terminal domain that helps recognize many substrates, either directly or by binding adaptor proteins, such as SspB. The ClpX N domain recognizes different sequence determinants in the C. crescentus and E. coli SspBs. The C. crescentus determinants span 10 residues and involve interactions with multiple side-chains, whereas the E. coli sequence is only five residues and has two important sidechain contacts. The ClpX N domain is clearly a highly versatile platform for peptide recognition that can function to expand ClpX's substrate repertoire.

195 Myoglobin strikes back

Maurizio Brunori

In the 60s, myoglobin was known as ‘the H atom of molecular biology’, and for more than half a century its structure has been an ideal and versatile model in protein science research. In the 90s, nitric oxide placed myoglobin center stage once again, with a fresh outlook on its physio-pathological role. In the new millennium, myoglobin has unveiled novel features of biochemical dynamics, being the main character on the (picosec-to-millisec) time-resolved Laue crystallography conformational landscape. The role this vital protein has played in protein science research are reviewed here.