The structure of human rhinovirus 3 at 3.0 A resolution
Abstract
Human Rhinovirus (HRV) is the major causative agent of the common cold in humans and consists of over 100 different serotypes. The crystal structures of HRV14 and HRV16, the major receptor group viruses, as well as HRV1A, a minor receptor group virus, have been previously determined. In this thesis, structural studies of HRV3, another major receptor group virus, were conducted in order to better understand the structure and function relationship in rhinoviruses. HRV3 was crystallized in space group P2$\sb1$22$\sb1$, and the structure was determined by the Molecular Replacement method using HRV14 as an initial model. The amino acid sequence of HRV3 capsid proteins was obtained through cDNA cloning of the HRV3 RNA genome. The structure and amino acid sequence of HRV3 are very similar to HRV14. The structure of HRV3 was compared with other rhinoviruses. A structural basis for the different antigenic properties and stability displayed by HRV3 was proposed, and the implications of the similarity between HRV3 and HRV14 was discussed. The structure of the HRV3+WIN56291 (an antiviral compound) complex was also studied. This structure is similar to HRV14+WIN56291 structure, which explains the similar efficacy of WIN56291 against these two rhinoviruses. The non-protein density on rhinovirus five-fold axes has been demonstrated to belong to an EGTA-chelatable ion. Analysis of the coordination geometry of these metal ions suggests that the ions in HRV3, HRV14, and HRV1A are Ca$\sp{++}$ ions, and the ion in HRV16 is Zn$\sp{++}$. The structure of HRV16 empty particles was studied using difference maps between empty and native particles. The maps showed dramatic disordering of the N-termini of VP1 and VP2 in the empty particles, although details of these conformational changes could not be determined until more diffraction data are available on HRV16 empty particles.
Degree
Ph.D.
Advisors
Rossmann, Purdue University.
Subject Area
Microbiology|Biophysics|Biochemistry
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