Biology subjects

Mathew, M. K.

Publications and source records attributed to Mathew, M. K..

4 recordsLinked to original sources

bioRxiv2025

The longer transmembrane helices of class I viral fusion proteins may facilitate viral fusion

The viral envelope-resident viral fusion proteins (VFPs) fuse the envelope with the host cell membrane, which allows virus entry into host cells. The homotrimeric class I VFPs (cI-VFPs) are anchored to the envelope by three single-pass transmembrane helices (spTMHs). It is generally accepted that the hydrophobic length of a TMH matches the thickness of the hydrophobic membrane core, and this reduces TMH dynamics by stabilizing both the TMHs and the membrane. However, to enable fusion, a cI-VFP undergoes a large conformational transition which includes the disassembly of the spTMHs from a pre-fusion trimer and their subsequent reassembly with the cI-VFP fusion peptides into a post-fusion complex. Given the potential functional relevance of the cI-VFP spTMH disassembly-reassembly dynamics, we hypothesized that these spTMH lengths may be mismatched with the thickness of biological membranes. Here, we examine the predicted lengths of a curated dataset of cI-VFP spTMHs and find that they are indeed about 10% longer than the hydrophobic thickness of model membranes. The cI-VFP spTMHs are on average also longer than the spTMHs of human fusion and human non-fusion proteins. Since our dataset contains cI-VFPs from diverse enveloped viruses, and viral proteins are fast evolving, we conclude that the longer spTMHs are functionally relevant and thus, preserved. Our observation that the spTMH lengths of retrovirus-derived human fusogenic proteins, syncytins, are similar to those of cI-VFPs, supports this conclusion. The longer spTMHs may facilitate the cI-VFP conformational change and perturb the fusing membrane, reducing the barrier to fusion.

biochemistry↗

bioRxiv2023

Fluid Uptake Pathways Are Differentially Modified in Rice (Oryza sativa L.) in Response to Drought and Salinity

Salinity and drought adversely affect rice production globally. Here we have examined physiological responses to drought and salinity across four rice cultivars with varying sensitivity to these stresses. The salt tolerant Pokkali restricts fluid entry to limit Na+ uptake under saline stress, while the drought-tolerant ARB6 needs to enhance fluid uptake under drought. Surprisingly, Pokkali does reasonably well when subjected to drought as does ARB6 under saline stress - in contrast to the stress-sensitive but high yielding varieties IR-20 and Jaya. Both tolerant varieties use long roots to mine water under deficit conditions, increasing aerenchyma and suberization of the exodermis to provide oxygen to deep-reaching roots. Major alterations in patterns of suberization in both exodermis and endodermis are undertaken, the patterns being dramatically different under the two stresses. Genes implicated in suberin biosynthesis also showed variation in transcript levels under stress, corresponding with the observed suberization patterns. Osmolyte accumulation drives uptake of water under deficit conditions, while restricting fluid flow to symplastic routes minimizes Na+ entry. Overall, the morphological and physiological responses of the tolerant varieties ensure adequate fluid flow through the transpiration stream without excessive salt uptake, thereby promoting growth under both drought and salinity.

plant biology↗

bioRxiv2023

Highly Localized Responses to Salinity and Drought in Rice Roots

Drought and salt stress are first sensed by the root system of plants. Many physiological responses, including variation in stomatal conductance, are regulated by the stress hormone ABA which is generated in the root and sent up to the shoot which then synthesizes additional ABA to sustain the response. To address whether responses are systemic we have used a split root system, wherein roots are divided into two and each half treated independently to water, salt or drought. Four varieties were examined - the salt tolerant Pokkali, the drought tolerant ARB6 and two sensitive varieties Jaya and IR-20. ABA concentrations in the xylem sap increased dramatically after Day 1 in all four cultivars in response to stress on at least one side the of the split root system. The sensitive varieties appeared to derive much of their nutrition and fluid from the watered side when subjected to asymmetric conditions, whereas roots on the stressed side of tolerant varieties underwent anatomical and physiological modifications facilitating fluid uptake and maintenance of xylem sap flow under these conditions.

plant biology↗

bioRxiv2021

Dynamics and self-assembly of the SARS-CoV-2 spike transmembrane domain

The homotrimeric SARS-CoV-2 spike protein enables viral infection by mediating the fusion of the viral envelope with the host membrane. The spike protein is anchored to the SARS-CoV-2 envelope by its transmembrane domain (TMD), which is composed of three TM helices, each contributed by one of the protomers of the homotrimeric spike. Although the TMD is important for SARS-CoV-2 viral fusion and is well-conserved across the Coronaviridae family, it is unclear whether it is a passive anchor of the spike or actively promotes viral fusion. Specifically, the nature of the TMD dynamics and how these dynamics couple to the large pre- to post-fusion conformational transition of the spike ectomembrane domains remains unknown. Here, we computationally study the SARS-CoV-2 spike TMD in both homogenous POPC and cholesterol containing membranes to characterize its structure, dynamics, and self-assembly. Different tools identify distinct segments of the spike sequence as its TM helix. Atomistic simulations of a spike protomer segment that includes the superset of the TM helix predictions show that the membrane-embedded TM sequence bobs, tilts and gains and loses helicity at the membrane edges. Coarse-grained multimerization simulations using representative TM helix structures from the atomistic simulations exhibit diverse trimer populations whose architecture depends on the structure of the TM helix protomer. Multiple overlapping and conflicting dimerization interfaces stabilized these trimeric populations. An asymmetric conformation is populated in addition to a symmetric conformation and several in-between trimeric conformations. While the symmetric conformation reflects the symmetry of the resting spike, the asymmetric TMD conformation could promote viral membrane fusion through the stabilization of a fusion intermediate. Together, our simulations demonstrate that the SARS-CoV-2 spike TM anchor sequence is inherently dynamic, trimerization does not abrogate these dynamics and the various observed TMD conformations may enable viral fusion.

biophysics↗