Unravelling the inhibitory zinc ion binding site and the metal exchange mechanism in human DPP III

Dipeptidyl peptidase III (DPP III), a zinc-dependent exopeptidase, is widely distributed in organisms and present in almost all human tissues. In addition to its involvement in protein catabolism, it plays...

Recognizing Proteins with Binding Function in Elymus nutans Based on Machine Learning Methods

Background: We research the binding function proteins in Elymus nutans. Recognition for proteins is essential for study of biology. Machine learning methods have been widely used for the prediction of proteins. Methods: We used BLAST software for the function annotations of Elymus nutans. Besides, we used machine learning methods to recognize proteins which are not annotated by the software. In the process, we focused on identifying the proteins with binding functions. In our research, features are extracted by four algorithms, and then selected by mutual information estimator. Here three classifiers are constructed based on K-nearest neighbour algorithm and gradient boosting algorithm. Results and Conclusion: Experimental results show that there are 848 proteins with ATP binding function, 113 proteins with heme binding function, 315 proteins with zinc-ion binding function, 135 proteins with GTP binding function and 21 proteins with ADP binding function. Furthermore, we have successfully predicted the functions of 10 special protein sequences whose function annotations cannot be obtained by making sequence alignment with seven famous protein databases. Among them, seven sequences have ATP binding functions, one sequence has heme binding function, one sequence has zinc-ion binding function and the other one has GTP binding function.

Entropy-Based Analysis of Vertebrate Sperm Protamine Sequences: Evidence of Dityrosine and Cysteine-Tyrosine Cross-Linking in Sperm Protamines

BackgroundSpermatogenesis is the process by which germ cells develop into spermatozoa in the testis. Sperm protamines are small, arginine-rich nuclear proteins which replace somatic histones during spermatogenesis, allowing a hypercondensed DNA state that leads to a smaller nucleus and facilitating sperm head formation. In eutherian mammals, the protamine-DNA complex is achieved through a combination of intra- and intermolecular cysteine cross-linking and possibly histidine-cysteine zinc ion binding. Most metatherian sperm protamines lack cysteine but perform the same function. This lack of dicysteine cross-linking has made the mechanism behind metatherian protamines folding unclear.ResultsProtamine sequences from UniProt’s databases were pulled down and sorted into homologous groups. Multiple sequence alignments were then generated and a gap weighted relative entropy score calculated for each position. For the eutherian alignments, the cysteine containing positions were the most highly conserved. For the metatherian alignment, the tyrosine containing positions were the most highly conserved and corresponded to the cysteine positions in the eutherian alignment.ConclusionsHigh conservation indicates likely functionally/structurally important residues at these positions in the metatherian protamines and the correspondence with cysteine positions within the eutherian alignment implies a similarity in function. One explanation is that the metatherian protamine structure relies upon dityrosine cross-linking between these highly conserved tyrosines. Also, the human protamine P1 sequence has a tyrosine substitution in a position expecting eutherian dicysteine cross-linking. Similarly, some members of the metatherian Planigales genus contain cysteine substitutions in positions expecting plausible metatherian dityrosine cross-linking. Rare cysteine-tyrosine cross-linking could explain both observations.

Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation

The density-regulated protein (DENR) and the malignant T cell-amplified sequence 1 (MCT-1/MCTS1) oncoprotein support noncanonical translation initiation, promote translation reinitiation on a specific set of mRNAs with short upstream reading frames, and regulate ribosome recycling. DENR and MCT-1 form a heterodimer, which binds to the ribosome. We determined the crystal structure of the heterodimer formed by human MCT-1 and the N-terminal domain of DENR at 2.0-Å resolution. The structure of the heterodimer reveals atomic details of the mechanism of DENR and MCT-1 interaction. Four conserved cysteine residues of DENR (C34, C37, C44, C53) form a classical tetrahedral zinc ion-binding site, which preserves the structure of the DENR’s MCT-1–binding interface that is essential for the dimerization. Substitution of all four cysteines by alanine abolished a heterodimer formation. Our findings elucidate further the mechanism of regulation of DENR-MCT-1 activities in unconventional translation initiation, reinitiation, and recycling.

A ratiometric fluorescent molecular probe with enhanced two-photon response upon Zn2+ binding for in vitro and in vivo bioimaging

The ratiometric two-photon (2P) probe GBC shows enhanced 2P activity upon zinc ion binding and has been used for zinc ion imaging in vitro and in vivo.