Understanding Ubl-rpn1 Intermolecular Interaction - Understanding Ubl-rpn1 Intermolecular Interaction - Open Access Pub

ALS is the neurodegenerative disease which is caused due to breakdown in interaction between UBL and rpn1. In this study, we explore the interaction of UBL and rpn1 which is involved in protein degradation. Protein recycling system plays a crucial role in degradation of deformed or damaged proteins. Task of degradation of damaged ubiquitinated proteins is completed by proteasome with the help of ubiquilin2 protein which links 19s proteasome and poly-Ub chain attached to damaged protein. More specifically, N-terminal UBL domain interacts with rpn1 subunit of base complex of 19s proteasome and C-terminal UBA domain interacts with tetra poly-Ub chain attached to damaged protein. In present study, UBL domains are docked against homology modeled rpn1 with the help of Patch dock server. Further the docked structures are refined using fire dock server and best docked structure is chosen having global energy -16.71. Best docked structures are analyzed using swiss-pdb viewer software to show hydrogen bonds between interacting proteins. Here we explore a mutation E6A and P11A in UBL structure with the help of YASARA which is significantly increasing the interaction between interacting proteins in terms of hydrogen bonds. DOI10.14302/issn.2328-0182.japst-13-288 Amyotrophic lateral sclerosis (ALS), often referred to as "Lou Gehrig's Disease," is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed. Northwestern researchers have identified a link between ubiquilin-2 and the dominantly inherited chromosome X-linked Amyotrophic lateral sclerosis (ALS) and ALS/dementia. They discovered that ubiquilin 2, which is member of the ubiquilin family, regulates the degradation of ubiquitinated proteins. They show that mutations in UBQLN2 lead to an impairment of protein degradation. Ubiqulin 2 abnormalities are associated with abnormal protein aggregation and neurodegneration, revealing a common pathogenic mechanism that can be exploited for therapeutic intervention, including therapeutic screening and risk assessment of ALS and ALS-related diseases. Ubiquilin-2 is a protein that in humans is encoded by the