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Principal Investigator: JEAN S BAUM
Organization: RUTGERS, THE STATE UNIV OF N.J.
Fiscal Year: 2024
Award: $33,060
Funding agency: National Institute of General Medical Sciences
Abstract
The overarching goal in this proposal is to understand how molecular motions and biophysical properties
modulate protein interactions to promote normal homeostasis or pathological disease states. We investigate the
relationship between protein dynamics and interactions in three contexts: 1) protein–fibrillar collagen interactions
involved in platelet aggregation; 2) α-synuclein (αS), an intrinsically disordered protein (IDP) whose misfolding
and aggregation into amyloid fibrils and deposition into Lewy bodies are associated with debilitating
synucleinopathies, such as Parkinson’s Disease; and 3) the spike glycoprotein of the severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2), whose interaction with angiotensin converting enzyme 2 (ACE2) via the
receptor binding domain (RBD) is the initial point of host cell entry. We have recently discovered that in each of
these cases, conformational dynamics profoundly impact their atomic-to-nano scale properties and may affect
their potential for biomolecular interactions. Despite the biological importance of these systems and the
implications for their interactions on disease, the molecular determinants of these protein–protein interactions
remain unanswered. Thus, we use a multifaceted approach integrating solution and solid-state NMR with
biophysical, biological, and computational methods to address how molecular motions modulate protein
interactions to promote normal homeostasis or pathological disease states. Gaining a molecular understanding
of protein–protein interactions with each of these dynamic systems relies on state-of-the-art solution NMR
instrumentation to be able to accurately measure timescales and fluctuations of these interaction events and to
detect transient, lowly populated complexes.
Terms: <2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><ACE2><Address><Affect><Amyloid Fibrils><Amyloid deposition><Autoregulation><Biological><Biophysics><COVID-19 S protein><COVID-19 spike><COVID-19 spike glycoprotein><COVID-19 spike protein><Cell Body><Cell Function><Cell Physiology><Cell Process><Cells><Cellular Assay><Cellular Function><Cellular Physiology><Cellular Process><Collagen Fibril><Complex><Computing Methodologies><Disease><Disorder><Event><Fibrillar Collagen><Goals><Health><Homeostasis><Intervention><Intervention Strategies><Lewy Bodies><Measures><Mediating><Molecular><Molecular Configuration><Molecular Conformation><Molecular Stereochemistry><Motion><NAC precursor><PARK1 protein><PARK4 protein><Paralysis Agitans><Parkinson><Parkinson Disease><Pathologic><Physiological Homeostasis><Platelet aggregation><Primary Parkinsonism><Property><Protein Dynamics><Proteins><Reader><SARS-CoV-2 S><SARS-CoV-2 S protein><SARS-CoV-2 spike><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SNCA><SNCA protein><SSNMR><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Subcellular Process><System><Therapeutic><a-syn><a-synuclein><alpha synuclein><alpha synuclein gene><alphaSP22><angiotensin converting enzyme 2><angiotensin converting enzyme II><asyn><biologic><biophysical characteristics><biophysical characterization><biophysical equipment><biophysical foundation><biophysical measurement><biophysical parameters><biophysical principles><biophysical properties><biophysical sciences><biophysical tools><cell assay><computational methodology><computational methods><computer based method><computer methods><computing method><conformation><conformational><conformational state><conformationally><conformations><coronavirus disease 2019 S protein><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><design><designing><dynamic system><dynamical system><instrumentation><interventional strategy><monomer><nano meter scale><nano meter sized><nanometer scale><nanometer sized><nanoscale><non A-beta component of AD amyloid><non A4 component of amyloid precursor><protein protein interaction><receptor binding><receptor bound><self assembly><solid state NMR><solid state nuclear magnetic resonance><spike proteins on SARS-CoV-2><synucleinopathy><α synuclein gene><α-syn><α-synuclein>