Biology subjects

Huang, S.-J.

Publications and source records attributed to Huang, S.-J..

4 recordsLinked to original sources

bioRxiv2023

Can motional dynamics account for the cytotoxicity of beta amyloid oligomers?

The underlying biophysical principle governing the cytotoxicity of the oligomeric aggregates of {beta}-amyloid (A{beta}) peptides has long been an enigma. Here we show that the size of A{beta}40 oligomers can be actively controlled by incubating the peptides in reverse micelles. Our approach allowed for the first time a detailed comparison of the structures and dynamics of two A{beta}40 oligomers of different size, viz., 10 and 23 nm, by solid-state NMR. From the chemical shift data, we infer that the conformation of the residues from K16 to K28 are different between the 10-nm and 23-nm oligomers. We find that the 10-nm oligomers are more cytotoxic, and the molecular motions of their charged residues are more dynamic. Interestingly, the residue A21 exhibits an unusually high structural rigidity. Our data raise the interesting possibility that the cytotoxicity of A{beta}40 oligomers could also be correlated to the motional dynamics of the charged residues.

biophysics↗

bioRxiv2022

The 24-chain core-shell nanostructure of wood cellulose microfibrils in seed plants

Wood cellulose microfibrils (CMFs) are the most abundant organic substance on earth, but their nanostructures are poorly understood. There are controversies regarding the glucan chain number (N) of CMFs during initial synthesis and whether they become fused afterwards. Here, we combined small-angle X-ray scattering (SAXS), solid-state nuclear magnetic resonance (ssNMR) and X-ray diffraction (XRD) analyses to resolve these controversies. We successfully developed SAXS measurement methods for the cross-section aspect ratio and area of the crystalline-ordered CMF core, which showed higher density than the semi-disordered shell. The 1:1 aspect ratio suggested that CMFs remain mostly segregated, not fused. The area measurement revealed the chain number in the core zone (Ncore). The ratio of ordered cellulose over total cellulose, termed Roc, was determined by ssNMR. Using the formula N = Ncore / Roc, we found that the majority of wood CMFs contain 24 chains, conserved between gymnosperm and angiosperm trees. The average wood CMF has a crystalline-ordered core of [~]2.2 nm diameter and a semi-disordered shell of [~]0.5 nm thickness. In naturally and artificially aged wood, we only observed CMF aggregation (contact without crystalline continuity) but not fusion (forming conjoined crystalline unit). This further argued against the existence of partially fused CMFs in new wood, overturning the recently proposed 18-chain fusion hypothesis. Our findings are important for advancing wood structural knowledge and more efficient utilization of wood resources in sustainable bio-economies.

plant biology↗

bioRxiv2020

Molecular insights into substrate recognition and discrimination by the N-terminal domain of Lon AAA+ protease

The Lon AAA+ proteases (LonA) is a ubiquitous ATP-dependent proteolytic machine, which selectively degrades damaged proteins or native proteins carrying exposed motifs (degrons). Here we characterize the structural basis for substrate recognition and discrimination by the N-terminal domain (NTD) of LonA. The results reveal that the six NTDs are attached to the hexameric LonA chamber by flexible linkers such that the formers tumble independently of the latter. Further spectral analyses show that the NTD selectively interacts with unfolded proteins, protein aggregates, and degron-tagged proteins by two hydrophobic patches of its N-lobe, but not intrinsically disordered substrate, -casein. Moreover, the NTD selectively binds to protein substrates when they are thermally induced to adopt unfolded conformations. Collectively, our findings demonstrate that NTDs enable LonA to perform protein quality control to selectively degrade proteins in damaged states and suggest that substrate discrimination and selective degradation by LonA are mediated by multiple NTD interactions. Impact StatementThe N-terminal domains enable Lon protease to discriminate and capture selected protein species for degradation by exposed hydrophobic patches and flexible linkages to the hexameric core complex.

biochemistry↗

bioRxiv2018

Low Level LASER Therapy Induces Therapeutic Angiogenesis in Diabetic Mice with Hindlimb Ischemia

Patients with diabetes mellitus (DM) are at high risk of developing peripheral arterial obstructive disease (PAOD) in lower extremities. Previous studies show low level LASER therapy (LLLT) can increase angiogenesis in vivo and in vitro. Here we performed hindlimb ischemia as PAOD model on diabetic mice to test the effects of LLLT. Twenty C57Bl/6 mice were randomly divided into four groups. Control group mice received femoral artery ligation/excision only. DM group mice were injected with Streptozocin (STZ) to induce diabetes followed by femoral artery ligation/excision. LLLT group mice received femoral artery ligation/excision and the lower limbs received LASER treatment for five days (660nm, 10 min, 1.91 J/cm2) started from second day postoperatively. DM+LLLT group mice were received femoral artery ligation/excision and LASER treatment after diabetes induced. Three days after LASER treatment finished, limb blood flow was measured by Laser Doppler perfusion imaging. Capillary density was assessed by immunofluorescence staining. CD31, VEGF, HIF-1, phospho-ERK, iNOS and eNOS protein level was examined by Western blot. Blood perfusion, capillary density, CD31, and VEGF protein levels were significantly higher in those groups received LLLT compared to control and DM group. Low level LASER significantly increased ERK phosphorylation and HIF-1 expression. In addition, phospho-eNOS was increased but iNOS protein level was decreased in mice received LASER treatment. In summary, the ability of low level LASER to induce therapeutic angiogenesis in diabetic mice suggested this approach deserves investigation as a novel approach to treat PAOD patients.

physiology↗