Crystal structure of human Gadd45γ corrected reveals an active dimer

The human Gadd45 protein family plays critical roles in DNA repair, negative growth control, genomic stability, cell cycle checkpoints and apoptosis. Here we report the crystal structure of human Gadd45γ [corrected], revealing a unique dimer formed via a bundle of four parallel helices, involving the most conserved residues among the Gadd45 isoforms. Mutational analysis of human Gadd45γ [corrected] identified a conserved, highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen (PCNA), p21 and cdc2, suggesting that the parallel dimer is the active form for the interaction. Cellular assays indicate that: (1) dimerization of Gadd45γ [corrected] is necessary for apoptosis as well as growth inhibition, and that cell growth inhibition is caused by both cell cycle arrest and apoptosis; (2) a conserved and highly acidic patch on the dimer surface, including the important residues Glu87 and Asp89, is a putative interface for binding proteins related to the cell cycle, DNA repair and apoptosis. These results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function.

Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its αNAC subunit

Nascent polypeptide associated complex (NAC) and its two isolated subunits, αNAC and βNAC, play important roles in nascent peptide targeting. We determined a 1.9 Å resolution crystal structure of the interaction core of NAC heterodimer and a 2.4 Å resolution crystal structure of αNAC NAC domain homodimer. These structures provide detailed information of NAC heterodimerization and αNAC homodimerization. We found that the NAC domains of αNAC and βNAC share very similar folding despite of their relative low identity of amino acid sequences. Furthermore, different electric charge distributions of the two subunits at the NAC interface provide an explanation to the observation that the heterodimer of NAC complex is more stable than the single subunit homodimer. In addition, we successfully built a βNAC NAC domain homodimer model based on homologous modeling, suggesting that NAC domain dimerization is a general property of the NAC family. These 3D structures allow further studies on structure-function relationship of NAC.

The correlation between heart rate turbulence of pediatric viral myocarditis and other indexes / 中国基层医药

Objective To study the value of heart rate turbulence(HRT) of acute pediatric viral myocarditis (VMC) ,and the relationship between HRT and other indexes. Methods We randomly assigned 75 acute pediatric VMC and 77 health enfant those all received holter. We calculated the heart rate turbulence(To) and turbulence slope (Ts) respectively,and compared the difference between them. Simultaneously, record the number of ventricular pre-mature complex(VPC) ,whether with ventricular tachycardia(VT) and the SDNN index of HRV. Then we analyzed the association between them and To,Ts. Results The difference of To between pediatric VMC and control group is significant in statistics, as follows [ (1.47±2.03 ) %, (-0.78±2.55) %, P<0.01; (3.05±2.12) ms/RR, (8.82±3.42) ms/RR,P<0.01]. There are no correlation between To and the number of VPC. And the number of VPC is interrelated to Ts. To and Ts are not correlative with whether with VT and heart rate variability(HRV). Conclusions The HRT of pediatric VMC is significanty reduced,so HRT can be a new index that to evaluate the heart parasym-pathetic function state in pediatric VMC and it is independent from traditional HRV. Therefore we can evaluate the heart parasympathetic function state of the sufferers after analyzed their HRT. This technique can help to discover pathological changes of heart parasympathetic system in forepart and guide clinical therapy in time,and avoid heart ill event.