Research highlights

Protein Function - Allostery goes dynamic

We have discovered a very intriguing mechanism that calls for revision of our fundamental understanding of the mechanisms that underlie protein function and regulation. Our study suggests that the notion of purely structurally regulated activity in allosteric proteins should be revised to include a frequently dominating contribution from protein dynamics. We have characterized cAMP binding to CAP. We find, surprisingly, that even when in a structurally inactive conformation, CAP can be activated for ligand (DNA) binding by changes in protein dynamics. These results are now published in Nature. Read the Editor's summary. Read the manuscript.

Gene Regulation - Structural basis for cAMP-mediated activation of CAP

We have determined the solution structure of the catabolite activator protein (CAP) in the absence of cAMP. The structure, together with previously determined structures of CAP in the presence of cAMP and DNA, provide the complete structural basis for cAMP-mediated allosteric activation of CAP. These results are now published in Proc. Natl. Acad. Sci. USA. Download the article. See also a movie.

Ma and Nussinov wrote a commentary in PNAS entitled “Amplification of signaling via cellular allosteric relay and protein disorder”. Download the commentary. Donwload a research highlight. Faculty1000 evaluation.

Protein Secretion - Structural basis for signal sequence recognition

Recognition of signal sequences by cognate receptors is a decisive step in correctly sorting secretory from nonsecretory proteins. We have determined the solution structure of a secretion signal sequence in complex with an essential bacterial receptor, SecA, the 204-kDa ATPase motor of the Sec translocase machinery. The combined data not only explain how SecA may achieve the promiscuous recognition of a large set of signal sequences, but also provide insight into how the Sec nanomachinery may ultimately be assembled. These results are now published in Cell. Download the article

Rated as "Exceptional" by Faculty 1000. Read the evaluation

Signal Transduction - Control by proline isomerization

We have shown that autoinhibition can be controlled by an intrinsic intramolecular switch afforded by prolyl cis-trans isomerization. Peptidyl-prolyl isomerase enzymes such as cyclophilin A accelerate the slow cis-trans intervonversion rate. Proline isomerization appears to make an ideal switch that can regulate the kinetics of activation, thereby modulating the dynamics of signal response. These results are now published in Molecular Cell. Download the article

Nicholson & Ping Lu wrote a Preview entitled "Prolyl cis-trans isomerization as a molecular timer in Crk signaling". Download the Preview

Protein Allostery - It can be dynamically mediated

We have shown that allosteric interactions can be mediated exclusively by transmitted changes in protein motions, in the absence of conformational changes. Our results provide strong support of the existence of purely dynamics-driven allostery. These data are now published in Nature Structural & Molecular Biology. Download the article

Lewis Kay discussed our paper in the "Journal Club" of Nature; "The molecular dance of a protein allows a chemist's secret wish to come true". Download the highlight

Protein Secretion - SecA helicase motor properties

SecA is an exquisitely designed and engineered protein motor that recognizes secretory proteins and couples their transport through the transmembrane SecYEG channel to ATP binding and hydrolysis. Using an integrated NMR, thermodynamic, and biochemical approach we have discovered a novel mechanism that underlies its function. The results are published in Nature Structural & Molecular Biology (article of the month). Download the article

John Hunt and coworkers wrote a News & Views entitled "Disorder breathes life into a DEAD motor". Download the News & Views

Transcription Regulation - Structural basis

Sequence-specific protein-DNA interactions are responsible for the regulation of key biological functions such as replication of the genome, initiation of transcription, and repair of damaged DNA. We have recently provided the structural and dynamic basis of the 
complete recognition pathway of the lac repressor system. The results have been published in Science. Download the article

Peter von Hippel wrote a nice Perspective entitled "Completing the view of transcriptional regulation". Download the Perspective