SynopsisThe amino-terminal telopeptide of the collagen al(1) chain has a highly conserved sequence. This sequence was analyzed by the Chou-Fasman criteria, and a folded P-sheet conformation, including a P-turn, was predicted. This folded "hairpin" region favors both ionic and hydrophobic intermolecular interactions with al(1) chain residues 930-938 on a neighboring, end-overlapped molecule. An end-overlap interaction of this nature could direct the initial step in fibril formation. The predicted structure also places the potential crosslink-forming lysyl residue, gN, in a unique site a t the /3-turn end of the telopeptide.The type I collagen molecule exists as a long, stiff rod, 15 X 3000 A, composed of two identical al(1) chains and a nonidentical a2 chain. The al(1) chain is 1055 amino acids long; the characteristic triple-helix-forming sequence of repeating -Gly-X-Y-(where X is frequently proline and Y is frequently hydroxyproline) extends over the central 1014 residues.l Short non-triple-helix-forming sequences, called telopeptides,2 comprise the first 16 residues a t the amino terminal of al(1) chain and the last 25 residues at the carboxyl terminal. The telopeptides are rich in tyrosine, which does not occur in the triple-helical region. Each telopeptide contains a lysyl residue which is a potential crosslink precursor after enzymic oxidation to an aldehyde. The telopeptides are susceptible to several proteinases which cannot attack the triple-helical portion of the collagen m~l e c u l e .~-~ Interstitial collagen fibers exhibit a 670-w axial periodicity D, which has been measured both by x-ray diffraction and by electron microscopy. In the generally accepted two-dimensional repre~entation,~ each molecule, -4.40 in length, is displaced axially by 1D from each of its nearest neighbors, leaving an 0.6D gap between axially aligned molecules. The early four-strand6 and five-strand7 microfibril models, as well as more recent analyses,s-10 were designed to preserve the Hodge-Petruska 1D stagger in a three-dimensional ropelike array. The microfibril concept has received verification in small-and medium-angle x-ray diffraction studies of tendons'l and reconstituted collagen fibrils.12

Phosphophoryn (PP) is a protein unique to the mineralized matrix of dentin. It also has a unique composition, with aspartic acid and phosphoserine comprising greater than 85% of all amino acid residues. Because of this unique composition and high content of phosphoserine, it has been difficult to apply direct peptide sequencing procedures effectively. However, to understand its function, and to prepare suitable probes for screening cDNA libraries, some sequence distribution information is required. To this end, using bovine (b) and rat incisor (ri) PPs, partial mild acid hydrolysis has been used to cleave at the aspartic acid residues and generate free amino acids and small peptides. The nature of the released amino acids and peptides has been determined. Peptides have also been generated by limited digestion with trypsin. Some of the peptides have been purified by h.p.l.c. techniques and sequenced. About 90% of the bPP and riPP were resistant to trypsin, and the large resistant fragment was sharply depleted of the non-aspartic acid and non-phosphoserine [(P)Ser] residues. All peptides isolated were acidic, but the remaining residues (other than aspartic acid and serine) appeared to be collected in regions flanking the trypsin-resistant core. These data show directly the presence of regions [Asp]n, [(P)Ser]m and [Asp-(P)Ser-Asp]k as prominent sequence features. A domain structure model is proposed.

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Several additions to a classroom activity are proposed in which an “enzyme” (the student) converts “substrates” (nut−bolt assemblies) into “products” (separated nuts and bolts) by unscrewing them.

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Physical models of differing molecular geometry were formed and hung on a Christmas tree to celebrate the holiday in an introductory college chemistry class.

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Macrophages play critical roles in maintaining tissue homeostasis and modulating immune responses. In response to microenvironmental cytokines, macrophages coordinate cellular signaling networks and diverse transcriptional programs to dictate their phenotypical and functional heterogeneity. For instance, LPS/IFNγ and IL-4 induce classically (M1) and alternatively (M2) activated macrophages, respectively. Remodeling cellular metabolism has been highlighted a key process underlying macrophage functional polarization. However, the precise mechanisms coordinating macrophage metabolism and polarization remain elusive. We report here that the kinase LKB1, a well-known negative regulator of mTOR signaling pathway, serves as a metabolic checkpoint that connects cellular metabolic reprogramming to functional polarization in macrophages. We found that genetic depletion of LKB1 in macrophages polarized their differentiation towards M2-like macrophages, characterized by enhanced expression of M2-associated markers, independently of mTOR and STAT6 signaling pathways. In contrast, loss of LKB1 had no substantial impact on M1-like macrophages. Moreover, LKB1-defienct macrophages orchestrated reprogramming of mitochondrial metabolism to facilitate M2 polarization and tumor immune evasion. Collectively, our studies establish a previously unappreciated role for LKB1 in connecting macrophage metabolism and functional polarization in modulating tumor immunity. This work was partially supported by the Herman B Wells Center and Riley Children’s Foundation.