Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens

Abstract Background In the course of infection, viruses such as HIV-1 must enter a cell, travel to sites where they can hijack host machinery to transcribe their genes and translate their proteins, assemble, and then leave the cell again, all while evading the host immune system. Thus, successful infection depends on the pathogen's ability to manipulate the biological pathways and processes of the organism it infects. Interactions between HIV-encoded and human proteins provide one means by which HIV-1 can connect into cellular pathways to carry out these survival processes. Results We developed and applied a computational approach to predict interactions between HIV and human proteins based on structural similarity of 9 HIV-1 proteins to human proteins having known interactions. Using functional data from RNAi studies as a filter, we generated over 2000 interaction predictions between HIV proteins and 406 unique human proteins. Additional filtering based on Gene Ontology cellular component annotation reduced the number of predictions to 502 interactions involving 137 human proteins. We find numerous known interactions as well as novel interactions showing significant functional relevance based on supporting Gene Ontology and literature evidence. Conclusions Understanding the interplay between HIV-1 and its human host will help in understanding the viral lifecycle and the ways in which this virus is able to manipulate its host. The results shown here provide a potential set of interactions that are amenable to further experimental manipulation as well as potential targets for therapeutic intervention

Object manipulation and tool use in Nicobar long-tailed macaques (Macaca fascicularis umbrosus)

This is an accepted manuscript of an article published by Springer in International Journal of Primatology on 08/09/2020, available online: https://link.springer.com/article/10.1007%2Fs10764-020-00141-y The accepted version of the publication may differ from the final published version.Object manipulation and tool use by non-human primates have received considerable attention from primatologists and anthropologists, because of their broad implications for understanding the evolution of tool use in humans. To date, however, most of the studies on this topic have focused on apes, given their close evolutionary relationship with humans. In contrast, fewer studies on tool use and object manipulation have been conducted on monkeys. Documenting and studying object manipulation and tool use in species that are more distantly related to humans can provide a broader perspective on the evolutionary origins of this behaviour. We present a detailed description of toolaided behaviours and object manipulation by Nicobar long-tailed macaques ( Macaca fascicularis umbrosus ) living along the coastlines of Great Nicobar Island. We made observations from December 2018 to March 2019, using ad libitum and focal sampling methods. We observed behaviours related to object manipulation and tool use in six different behavioural contexts (foraging, hygiene, communication, play, selfdirected and self-hygiene behaviour) involving eight different types of objects, namely resonance rod, play object, rolling platform, scraping tool, dental groom, pounding substrate, leaves as grip pads and wipers, and stimulation tool. We observed that males were involved in tool use and object manipulation more frequently than females. Our results add to existing records of object manipulation, tool-use behaviour and tool variants displayed by non-human primates, showing that Nicobar macaques perform multiple and diverse tool-aided behaviours

Exploring Protein Conformational Diversity

The native state of proteins is composed of conformers in dynamical equilibrium. In this chapter, different issues related to conformational diversity are explored using a curated and experimentally based database called CoDNaS (Conformational Diversity in the Native State). This database is a collection of redundant structures for the same sequence. CoDNaS estimates the degree of conformational diversity using different global and local structural similarity measures. It allows the user to explore how structural differences among conformers change as a function of several structural features providing further biological information. This chapter explores the measurement of conformational diversity and its relationship with sequence divergence. Also, it discusses how proteins with high conformational diversity could affect homology modeling techniques.Fil: Monzon, Alexander Miguel. Universidad Nacional de Quilmes; ArgentinaFil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zea, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; ArgentinaFil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentin

A comparative analysis of KMT2D missense variants in Kabuki syndrome, cancers and the general population

Determining the clinical significance of germline and somatic KMT2D missense variants (MVs) in Kabuki syndrome (KS) and cancers can be challenging. We analysed 1920 distinct KMT2D MVs that included 1535 germline MVs in controls (Control-MVs), 584 somatic MVs in cancers (Cancer-MVs) and 201 MV in individuals with KS (KS-MVs). The proportion of MVs likely to affect splicing was significantly higher for Cancer-MVs and KS-MVs than in Control-MVs (p = 0.000018). Our analysis identified significant clustering of Cancer-MVs and KS-MVs in the PHD#3 and #4, RING#4 and SET domains. Areas of enrichment restricted to just Cancer-MVs (FYR-C and between amino acids 3043–3248) or KS-MVs (coiled-coil#5, FYR-N and between amino acids 4995–5090) were also found. Cancer-MVs and KS-MVs tended to affect more conserved residues (lower BLOSUM scores, p < 0.001 and p = 0.007). KS-MVs are more likely to increase the energy for protein folding (higher ELASPIC ∆∆G scores, p = 0.03). Cancer-MVs are more likely to disrupt protein interactions (higher StructMAn scores, p = 0.019). We reclassify several presumed pathogenic MVs as benign or as variants of uncertain significance. We raise the possibility of as yet unrecognised ‘non-KS’ phenotype(s) associated with some germline pathogenic KMT2D MVs. Overall, this work provides insights into the disease mechanism of KMT2D variants and can be extended to other genes, mutations in which also cause developmental syndromes and cancer