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 Ϸ 40.0 Å, b Ϸ 27.0 Å, c Ϸ 678 Å, ␣ Ϸ 89.2°, ␤ Ϸ 94.6°, ␥ Ϸ 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.x-ray ͉ fiber ͉ crystallography ͉ fibril ͉ extracellular matrix A lthough the general features of the structure of type I collagen have been known for a long time, the specific packing arrangement of collagen molecules in situ has remained difficult to define, despite a great deal of effort by many investigators (1-16) (the general organization of type I collagen is summarized in Fig. 5, which is published as supporting information on the PNAS web site). Recently, we approached this difficult structural problem by employing conventional crystallographic techniques in x-ray fiber diffraction experiments (13,17,18), culminating in an initial electron density map (13, 19) that allowed a crude look at some aspects of the supermolecular arrangement of collagen molecules in situ. Unfortunately, the high degree of disorder observed in the gap region of the electron density map precluded the fitting of a molecular model to the electron density; the gap region was largely uninterpretable. Without the structure of the gap region, it was impossible to determine the overall molecular arrangement of collagen molecules in situ, and therefore its potential for improving our understanding of the structural, developmental, and pathological function of the collagen fibril at the molecular level remained unrealized. We have subsequently integrated additional (nonoverlapping) intensity data into the structural determination process (b...

Our electron density map is the first obtained from a natural fiber using these techniques (more commonly applied to single crystal crystallography). It reveals the three-dimensional molecular packing arrangement of type I collagen and conclusively proves that the molecules are arranged on a quasihexagonal lattice. The molecular segments that contain the telopeptides (central to the function of collagen fibrils in health and disease) have been identified, revealing that they form a corrugated arrangement of crosslinked molecules that strengthen and stabilize the native fibril.

We study the effect of spins on searches for gravitational waves from compact binary coalescences in realistic simulated early advanced LIGO data. We construct a detection pipeline including matched filtering, signal-based vetoes, a coincidence test between different detectors, and an estimate of the rate of background events. We restrict attention to neutron star-black hole (NS-BH) binary systems, and we compare a search using nonspinning templates to one using templates that include spins aligned with the orbital angular momentum. To run the searches we implement the binary inspiral matched-filter computation in PYCBC, a new software toolkit for gravitational-wave data analysis. We find that the inclusion of aligned-spin effects significantly increases the astrophysical reach of the search. Considering astrophysical NS-BH systems with nonprecessing black hole spins, for dimensionless spin components along the orbital angular momentum uniformly distributed in ð−1; 1Þ, the sensitive volume of the search with aligned-spin templates is increased by ∼50% compared to the nonspinning search; for signals with aligned spins uniformly distributed in the range (0.7,1), the increase in sensitive volume is a factor of ∼10.

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Tissue factor is a cell-surface glycoprotein receptor which initiates the blood coagulation cascade after vessel injury by interacting with blood clotting factor VII/VIIa and which is implicated in various pathological processes. When bound to tissue factor, factor VII is readily converted to the active protease factor VIIa by trace amounts of factors Xa, IXa or VIIa. Human tissue factor consists of 263 residues, the first 219 of which comprise the extracellular region. We have determined the crystal structure of the extracellular region at a resolution of 2.2 A. Tissue factor consists of two immunoglobulin-like domains associated through an extensive, novel, interdomain interface region. The binding site for factor VII lies at the interface region and involves residues from domain 1 and an extended loop (binding 'finger') of domain 2. This is the first reported structure of a representative of the class 2 cytokine receptor family, which also includes interferon-alpha, interferon-gamma (refs 2, 3) and interleukin-10 (ref. 4) receptors.

Collagen molecules in native 66.8 nm (D) periodic fibrils are widely believed to be assembled into discrete, rope-like substructures, or microfibrils. Several types of microfibril have been proposed (2, 4, 5, 7- and 8-stranded) mainly on the basis of information contained in the medium angle X-ray diffraction patterns of native tendon fibres. These patterns show a series of equatorial and near-equatorial Bragg reflections which indicate that the collagen molecules are arranged on a three-dimensional crystalline lattice. The 4-stranded, 5-stranded and 8-stranded microfibrils are D-periodic with approximate diameter 3.8 nm, and these and the 2-stranded model are supposed to be packed on a three-dimensional lattice whose basal unit cell, (approximately) perpendicular to the fibril axis, is tetragonal (or quasi-tetragonal)with side a, a square root 2 or 2a, where a is approximately 3.8 nm. In this paper we describe a re-interpretation of the X-ray data which leads to a new model for the crystalline regions of the fibril, based on quasi-hexagonal molecular packing without microfibrillar sub-structures, and hence having the character of a molecular crystal.

Small‐angle scattering studies on biological structures provide low‐resolution models. More detailed models need a more elaborate analysis in order to show their uniqueness. The representation of small‐angle scattering of both in Cartesian coordinates and polar coordinates is discussed. The degree of non‐uniqueness of structural analysis is best presented in terms of a multipole expansion. Contrast variation leads to the evaluation of the basic scattering functions Jc(κ), Jcs(κ) and Js(κ), which add useful constraints to a model. The experimental aspects of this method in both X‐ray and neutron scattering are discussed. Furthermore, isomorphous (or isotopic) replacement of parts of macromolecular structures have been very useful in structure determination of ribosomes. Kinetic investigations of solutions in the subsecond region have been performed so far only for the investigation of H–D exchange with some proteins. Small‐angle scattering from fibrous and lamellar systems received a considerable impact from a combined use of X‐ray and neutron scattering, as is shown for collagen. Structural changes during active muscle contraction have been investigated both with classical X‐ray equipment and with synchrotron radiation.