A Model for the Three-Dimensional Structure of Human Plasma Vitronectin from Small-Angle Scattering Measurements
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- 作者：Gary W. Lynn ; William T. Heller ; Anand Mayasundari ; Kenneth H. Minor ; and Cynthia B. Peterson
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：January 18, 2005
- 年：2005
- 卷：44
- 期：2
- 页码：565 - 574
- 全文大小：1066K
- 年卷期：v.44,no.2(January 18, 2005)
- ISSN：1520-4995
文摘
Small-angle X-ray scattering (SAXS) measurements were used to characterize vitronectin, acirculatory protein found in human plasma that functions in regulating cell adhesion and migration, aswell as proteolytic cascades that affect blood coagulation, fibrinolysis, and pericellular proteolysis. SAXSmeasurements were taken over a 3-fold range of protein concentrations, yielding data that characterize amonodisperse system of particles with an average radius of gyration of 30.3 ± 0.6 Å and a maximumlinear dimension of 110 Å. Shape restoration was applied to the data to produce two models of the solutionstructure of the ligand-free protein. A low-resolution model of the protein was generated that indicatesthe protein to be roughly peanut-shaped. A better understanding of the domain structure of vitronectinresulted from low-resolution models developed from available high-resolution structures of the domains.These domains include the N-terminal domain that was determined experimentally by NMR [Mayasundari,A., Whittemore, N. A., Serpersu, E. H., and Peterson, C. B. (2004) J. Biol. Chem. 279, 29359-29366]and the docked structure of the central and C-terminal domains that were determined by computationalthreading [Xu, D., Baburaj, K., Peterson, C. B., and Xu, Y. (2001) Proteins: Struct., Funct., Genet. 44,312-320]. This model provides an indication of the disposition of the central domain and C-terminalheparin-binding domains of vitronectin with respect to the N-terminal somatomedin B (SMB) domain.This model constructed from the available domain structures, which agrees with the low-resolution modelproduced from the SAXS data, shows the SMB domain well separated from the central and heparin-binding domains by a disordered linker (residues 54-130). Also, binding sites within the SMB domainare predicted to be well exposed to the surrounding solvent for ease of access to its various ligands.