We have active collaborations with other laboratories to determine the structure of HK97 capsids and assembly intermediates in order to understand how the structures assemble and how the structures change during maturation. The long term goal of these studies is not only to discover what changes take place, but also to understand the mechanisms and purpose behind the maturational changes.
3D cryo-electron microscopy wiht Alasdair Steven's lab.
We have an active collaboration with Alasdair
C. Steven at the LABORATORY OF STRUCTURAL BIOLOGY,
National Institute of Arthritis and Musculoskeletal and Skin Diseases.
We have been studying the HK97 capsid structure using 3 dimensional
reconstructions from images made of well-preserved frozen-hydrated samples
using cryo-electron microscopy. Collaborators have included
James Conway, Naiqian Cheng and Ramani Kharidehal-Lata.
Much of this work has been published. Initial studies of HK97 head and assembly
intermediates appeared in
Conway, et al., 1995.
More recently we have examined the dynamics of maturation of HK97 Prohead II
as it transforms into Head II as described in Lata, et al.,2000.
This work resulted in the production of movies of the HK97 Prohead to Head transformation that are available on line
(HK97 Movies online).
We have an active collaboration with Jack Johnson's Lab at The Scripps Research Institute in La Jolla, CA. These include the completed HK97 Head II x-ray structure with Bill Wikoff, on-going sturctural and biochemical studies of the structures of HK97 expansion intermediates with Lu Gan (Gan, et al., 2004), fluorescence and small angle x-ray studies to monitor the dynamics of capsid structure during capsid maturation with Kelly Lee , (Lee, et al., 2005) and (Lee, et al., 2004), and ongoing work including crystallization trials of both Prohead I and Prohead II in collaboration with Lu Gan, Ilya Gertsman, and Rick Huang.
Bill Wikoff grew crystals of HK97 Head II that diffract x-rays beyond 3.5 * resolution and produced first crystallographic model of the hK97 mature empty capsid. A detailed model of the HK97 head based on the near-atomic resolution structure was published in