https://www.auburn.edu/academic/classes/biol/6190/refs/L04/1-s2.0-S0092867402009716-main.pdf

Integrins: Bidirectional, Allosteric Signaling Machines

Cell migration is a highly integrated multistep process that orchestrates embryonic morphogenesis; contributes to tissue repair and regeneration; and drives disease progression in cancer, mental retardation, atherosclerosis, and arthritis. The migrating cell is highly polarized with complex regulatory pathways that spatially and temporally integrate its component processes. This review describes the mechanisms underlying the major steps of migration and the signaling pathways that regulate them, and outlines recent advances investigating the nature of polarity in migrating cells and the pathways that establish it.

/pdf/cell-migration-integrating-signals-from-front-to-back-g0h3q2xs5i.pdf

Cell migration: integrating signals from front to back.

Collagen is the most abundant protein in animals. This fibrous, structural protein comprises a right-handed bundle of three parallel, left-handed polyproline II-type helices. Much progress has been made in elucidating the structure of collagen triple helices and the physicochemical basis for their stability. New evidence demonstrates that stereoelectronic effects and preorganization play a key role in that stability. The fibrillar structure of type I collagen—the prototypical collagen fibril—has been revealed in detail. Artificial collagen fibrils that display some properties of natural collagen fibrils are now accessible using chemical synthesis and self-assembly. A rapidly emerging understanding of the mechanical and structural properties of native collagen fibrils will guide further development of artificial collagenous materials for biomedicine and nanotechnology.

/pdf/collagen-structure-and-stability-4a8qztbno6.pdf

Collagen Structure and Stability

The structural basis for the divalent cation-dependent binding of heterodimeric alphabeta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the alphaV and beta3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. The tertiary rearrangements take place in betaA, the ligand-binding domain of beta3; in the complex, betaA acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of alphaV relative to beta3.

Crystal Structure of the Extracellular Segment of Integrin αVβ3 in Complex with an Arg-Gly-Asp Ligand

Integrins are cell adhesion molecules that mediate cell-cell, cell– extracellular matrix, and cell-pathogen interactions. They play critical roles for the immune system in leukocyte trafficking and migration, immunological synapse formation, costimulation, and phagocytosis. Integrin adhesiveness can be dynamically regulated through a process termed inside-out signaling. In addition, ligand binding transduces signals from the extracellular domain to the cytoplasm in the classical outside-in direction. Recent structural, biochemical, and biophysical studies have greatly advanced our understanding of the mechanisms of integrin bidirectional signaling across the plasma membrane. Large-scale reorientations of the ectodomain of up to 200 ˚ A couple to conformational change in ligand-binding sites and are linked to changes in α and β subunit transmembrane domain association. In this review, we focus on integrin structure as it relates to affinity modulation, ligand binding, outside-in signaling, and cell surface distribution dynamics.

/pdf/structural-basis-of-integrin-regulation-and-signaling-4crytzzf5r.pdf

Structural Basis of Integrin Regulation and Signaling

Identification of an α2β1-binding sequence in collagen I

/pdf/studies-on-the-hydroxylation-of-lysine-occurring-in-the-non-4ld18a5sfq.pdf

Studies on the hydroxylation of lysine occurring in the non-helical region at the N-terminal end of the collagen molecule.

https://portlandpress.com/biochemsoctrans/article-pdf/14/6/1086/508098/bst0141086.pdf

Platelet-reactive sites in collagens I and III

enzymatically catalyzed disulfide exchange Sustained integrin ligation involves extracellular free sulfhydryls and

Kortum and Weisbach (2021) propose a general equilibrium model for carbon taxation and derive the optimal policy as a function of marginal damages from emissions. This paper serves as an extension of Kortum and Weisbach by combining the general structure of Kortum and Weisbach with the Eaton and Kortum (2002) model of trade. Our results generalize Kortum and Weisbach to a multi-country world where the coalition consists of many heterogeneous countries. Like Kortum and Weisbach, our optimal policy consists of i) an extraction tax, ii) a partial border adjustment that partially shifts the tax imposition downstream and reduces leakage, and iii) an export policy that simultaneously exploits inelastic demand for goods amongst noncoalition countries and expands the export margin. Because the export policy functions as an external penalty incentivizing participation, we interpret coalitions implementing the optimal policy as climate clubs akin to those orignally proposed by Nordhaus (2015). We find that coalitions that implement the optimal unilateral policy can be unstable and that coalition instability has a considerable impact on the effectiveness of the optimal unilateral policy in reducing global emissions. I would like to express my sincerest gratitude to Professor Kortum, whose invaluable assistance, support, and mentorship over the past two years as my professor, research advisor, and thesis advisor made this paper possible. I would also like to thank my parents, sister, uncle, grandparents, and friends, including Chris, Robert, Mark, Daniel, and Michelle, who supported and encouraged me throughout this process. Finally, I’d like to thank Professor Patrick Devlin, who taught me to find curiosity at the intersection of rigor and intuition, and the late Bob Turansky, who taught me that knowledge without understanding is hollow. All errors are my own.

Michael J. Barnes

Papers

Identification of an α2β1-binding sequence in collagen I

Studies on the hydroxylation of lysine occurring in the non-helical region at the N-terminal end of the collagen molecule.

Platelet-reactive sites in collagens I and III

enzymatically catalyzed disulfide exchange Sustained integrin ligation involves extracellular free sulfhydryls and

Unilateral Carbon Policies and Multilateral Coalitions