Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Subtype Differences in the Interaction of HIV-1 Matrix with Calmodulin: Implications for Biological Functions
Biomolecules (Basel, Switzerland), v 11(9), p1294
31 Aug 2021
PMID: 34572507
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The HIV-1 Gag polyprotein plays essential roles during the late stage of the HIV-1 replication cycle, and has recently been identified as a promising therapeutic target. The N-terminal portion of the HIV-1 Gag polyprotein encodes the myristoylated matrix (MA) protein, which functions in the trafficking of the structural proteins to the plasma membrane (PM) and facilitation of envelope incorporation into budding virus. Numerous host cell proteins interact with the MA portion of the Gag polyprotein during this process. One such factor is the ubiquitous calcium-binding protein calmodulin (CaM), which interacts preferentially with myristoylated proteins, thereby regulating cell physiology. The exact role of this interaction is poorly understood to date. Atomic resolution structures revealed the nature of the CaM-MA interaction for clade B isolates. In this study, we expanded our knowledge and characterized biophysically and computationally the CaM interaction with MA from other HIV-1 clades and discovered differences in the CaM recognition as compared to the prototypical clade B MA, with significant alterations in the interaction with the MA protein from clade C. Structural investigation and in silico mutational analysis revealed that HIV-1 MA protein from clade C, which is responsible for the majority of global HIV-1 infections, interacts with lower affinity and altered kinetics as compared to the canonical clade B. This finding may have implications for additional altered interaction networks as compared to the well-studied clade B. Our analysis highlights the importance of expanding investigations of virus-host cell factor interaction networks to other HIV-1 clades.
Metrics
Details
- Title
- Subtype Differences in the Interaction of HIV-1 Matrix with Calmodulin: Implications for Biological Functions
- Creators
- Alexej Dick - Drexel UniversitySimon Cocklin - Drexel University
- Publication Details
- Biomolecules (Basel, Switzerland), v 11(9), p1294
- Publisher
- MDPI
- Grant note
- GM125396 / NIH HHS R01 AI150491 / NIAID NIH HHS NS089435 / NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000699307000001
- Scopus ID
- 2-s2.0-85114021958
- Other Identifier
- 991019168343904721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology