Structure determination of the IC3b protein from the human complement system and of proteins with immunological interest.

• Main Author: Lescar, Julien.
• Other Authors: School of Biological Sciences
• Format: Research Report
• Language: English
• Published: 2008
• Subjects: DRNTU::Science::Biological sciences::Human anatomy and physiology::Deoxyribonucleic acids
• Online Access: http://hdl.handle.net/10356/14224
• Institution: Nanyang Technological University

Integrins are cell surface receptors which play key roles in cell-cell, cell-extracellular matrix and cell-pathogen interactions. Moreover, their importance in tumor metastasis is increasingly appreciated. Integrins on circulating leukocytes are normally in a resting state of low adhesiveness, but can rapidly become activated in response to internal "inside-out" or external "outside-in" signals. Integrin molecules are formed by two non-covalently associated alpha and beta subunits, both type 1 membrane glycoproteins, with a globular ligand-binding "head" linked to two rod-like "legs". The crystal structureof the ectodomain of the alphaVbeta3 integrin revealed a compact V-shaped molecule having each leg markedly bent, thus orientating the headpiece towards the plasma membrane. Extensive analyses of electron microscopic (EM) images of alphaVbeta3 suggested that its compact form could represent a resting state and extension of the legs may be associated with activation. In association with activation, it was also suggested that the hybrid domain swings out with respect to the headpiece, a hypothesis later substantiated by X-ray crystallographic studies of a fragment of the alphaIIbbeta3 integrin, consisting of the beta-propeller from the alpha subunit and the PSI, alphaI, and hybrid domains from the beta subunit. The structures of I-EGF1, I- EGF2 and I-EGF3 however, were missing in these studies.