Microfibrillar structure of type I collagen in situ

doi:10.1073/pnas.0502718103

Microfibrillar structure of type I collagen in situ

*Center for Synchrotron Radiation Research and Instrumentation, Department of Biological, Chemical, and Physical Sciences, Illinois Institute of Technology, 3101 South Dearborn Street, Chicago, IL 60616;
^†Rosalind Franklin Structural Biology Laboratories, Department of Biochemistry, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064;
^§School of Biological and Environmental Sciences, University of Stirling, Stirling FK9 4LA, United Kingdom; and
^¶School of Optometry and Vision Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cathays Park, Cardiff CF10 3NB, Wales, United Kingdom

Edited by Douglas C. Rees, California Institute of Technology, Pasadena, CA, and approved April 23, 2006 (received for review April 3, 2005)

Abstract

The fibrous collagens are ubiquitous in animals and form the structural basis of all mammalian connective tissues, including those of the heart, vasculature, skin, cornea, bones, and tendons. However, in comparison with what is known of their production, turnover and physiological structure, very little is understood regarding the three-dimensional arrangement of collagen molecules in naturally occurring fibrils. This knowledge may provide insight into key biological processes such as fibrillo-genesis and tissue remodeling and into diseases such as heart disease and cancer. Here we present a crystallographic determination of the collagen type I supermolecular structure, where the molecular conformation of each collagen segment found within the naturally occurring crystallographic unit cell has been defined (P1, a ≈ 40.0 Å, b ≈ 27.0 Å, c ≈ 678 Å, α ≈ 89.2°, β ≈ 94.6°, γ ≈ 105.6°; reflections: 414, overlapping, 232, and nonoverlapping, 182; resolution, 5.16 Å axial and 11.1 Å equatorial). This structure shows that the molecular packing topology of the collagen molecule is such that packing neighbors are arranged to form a supertwisted (discontinuous) right-handed microfibril that interdigitates with neighboring microfibrils. This interdigitation establishes the crystallographic superlattice, which is formed of quasihexagonally packed collagen molecules. In addition, the molecular packing structure of collagen shown here provides information concerning the potential modes of action of two prominent molecules involved in human health and disease: decorin and the Matrix Metallo-Proteinase (MMP) collagenase.

Footnotes

^‡To whom correspondence should be sent at the * address. E-mail: orgel{at}iit.edu
Author contributions: J.P.R.O.O., A.M., and T.J.W. designed research; J.P.R.O.O. and T.C.I. performed research; J.P.R.O.O. contributed new reagents/analytic tools; J.P.R.O.O. analyzed data; and J.P.R.O.O., T.C.I., A.M., and T.J.W. wrote the paper.
↵ ‖ These two isolated patches of density at 0.6D and 0.8D were observed in the initial electron density map (F _o P _o) and did not form any part of the collagen molecules. However, attempts to build in this density (using two leucine-rich proteins from decorin model structure as a generic model for this density; data not shown) resulted in a significant deterioration of the R factor when modeled within normal occupancy ranges, and the diminishing effects of significantly lower molecular occupancies made it difficult to assess the accuracy of the modeled leucine-rich repeat’s relative position and orientation within the collagen packing matrix. These patches of density are diminished in size in the 2 F _o − F _c map.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 1Y0F and 1YGV).
Abbreviations:

Abbreviation:

ECM,

extracellular matrix.
Freely available online through the PNAS open access option.