A dual-specific, tetravalent immunoglobulin G-like molecule, termed dual variable domain immunoglobulin (DVD-Ig™), is engineered to block two targets. Flexibility modulates Fc receptor and complement binding, but could result in undesirable cross-linking of surface antigens and downstream signaling. Understanding the flexibility of parental mAbs is important for designing and retaining functionality of DVD-Ig™ molecules. The architecture and dynamics of a DVD-Ig™ molecule and its parental mAbs was examined using single particle electron microscopy. Hinge angles measured for the DVD-Ig™ molecule were similar to the inner antigen parental mAb. The outer binding domain of the DVD-Ig™ molecule was highly mobile and three-dimensional (3D) analysis showed binding of inner antigen caused the outer domain to fold out of the plane with a major morphological change. Docking high-resolution X-ray structures into the 3D electron microscopy map supports the extraordinary domain flexibility observed in the DVD-Ig™ molecule allowing antigen binding with minimal steric hindrance.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169030 | PMC |
| http://dx.doi.org/10.4161/mabs.24258 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lophine incorporated azo dye as a novel colorimetric sensor for multiple metal ions.
Spectrochim Acta A Mol Biomol Spectrosc
January 2025
Laboratory of Organic Chemistry, Tarsadia Institute of Chemical Science, Uka Tarsadia University, Maliba Campus, Gopal Vidyanagar, Bardoli-Mahuva Road, Tarsadi 394650 Surat Gujarat India. Electronic address:
A single molecule sensor for several analytes is indeed desired by the scientists around the world due to obvious advantages. In this report we present a new class of Lophine incorporated azo dyes that has capacity of differential colorimetric detection of several metal ions. Interestingly the sensor was found to have pH dependent selective response towards several metals.
View Article and Find Full Text PDFRegulation of anaplerotic enzymes by melatonin enhances resilience to cadmium toxicity in Vigna radiata (L.) R. Wilczek.
Plant Physiol Biochem
January 2025
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
Melatonin (Mel) is a tryptophan-derived (N-acetyl-5-methoxytryptamine) molecule. In the present study, role of Mel in the regulation of various anaplerotic enzymes is discussed in relation to N metabolism and H-ATPase activity in mung bean under Cd stress. The application of Mel to the Cd-stressed mung bean seedlings was remarkable in improving the activity of hexokinase (35.
View Article and Find Full Text PDFPan-neurofascin autoimmune nodoparanodopathy: A case report and literature review.
Medicine (Baltimore)
January 2025
Department of Neurology (Nerve-Muscle Unit), Reference Center for Neuromuscular Diseases "AOC," ALS Reference Center, University Hospitals of Bordeaux (Pellegrin Hospital), University of Bordeaux, Bordeaux, France.
Rationale: Locked-in syndrome (and its variant, completely locked-in state) generally has a high mortality rate in the acute setting; however, when induced by conditions such as acute inflammatory polyradiculoneuropathy, it may well be curable such that an attempt at cure should be systematically sought by clinicians.
Patient Concerns: A 52-year-old man presented with acute tetraparesia and areflexia, initially diagnosed as Guillain-Barré syndrome. Despite appropriate treatment, his condition deteriorated, evolving into a completely locked-in state.
Rare dual MYH9-ROS1 fusion variants in a patient with lung adenocarcinoma: A case report.
Medicine (Baltimore)
January 2025
Department of Respiratory and Critical Care Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong Province, China.
Rationale: ROS proto-oncogene 1 (ROS1) fusion is a rare but important driver mutation in non-small cell lung cancer, which usually shows significant sensitivity to small molecule tyrosine kinase inhibitors. With the widespread application of next-generation sequencing (NGS), more fusions and co-mutations of ROS1 have been discovered. Non-muscle myosin heavy chain 9 (MYH9) is a rare fusion partner of ROS1 gene as reported.
View Article and Find Full Text PDFFocused ultrasound therapy as a strategy for improving glioma treatment.
J Neurosurg
January 2025
Departments of1Neurological Surgery and.
The infiltrative and diffuse nature of gliomas makes complete resection unfeasible. Unfortunately, regions of brain parenchyma with residual, infiltrative tumor are protected by the blood-brain barrier (BBB), making systemic chemotherapies, small-molecule inhibitors, and immunotherapies of limited efficacy. Low-frequency focused ultrasound (FUS) in combination with intravascular microbubbles can be used to disrupt the BBB transiently and selectively within the tumor and peritumoral region.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!