The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. Streptococcus gordonii is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans. The fibrillar adhesin CshA is an important determinant of S. gordonii adherence, forming peritrichous fibrils on its surface that bind host cells and other microorganisms. CshA possesses a distinctive multidomain architecture comprising an N-terminal target-binding region fused to 17 repeat domains (RDs) that are each ∼100 amino acids long. Here, using structural and biophysical methods, we demonstrate that the intact CshA repeat region (CshA_RD1–17, domains 1–17) forms an extended polymeric monomer in solution. We recombinantly produced a subset of CshA RDs and found that they differ in stability and unfolding behavior. The NMR structure of CshA_RD13 revealed a hitherto unreported all β-fold, flanked by disordered interdomain linkers. These findings, in tandem with complementary hydrodynamic studies of CshA_RD1–17, indicate that this polypeptide possesses a highly unusual dynamic transitory structure characterized by alternating regions of order and disorder. This architecture provides flexibility for the adhesive tip of the CshA fibril to maintain bacterial attachment that withstands shear forces within the human host. It may also help mitigate deleterious folding events between neighboring RDs that share significant structural identity without compromising mechanical stability.

Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans. This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder. The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown. Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80–2.50 Å resolution. These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis. Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site. Collectively, this information significantly builds on our understanding of the core fucosylation process.

Type IV filaments (T4F), which are helical assemblies of type IV pilins, constitute a superfamily of filamentous nanomachines virtually ubiquitous in prokaryotes that mediate a wide variety of functions. The competence (Com) pilus is a widespread T4F, mediating DNA uptake (the first step in natural transformation) in bacteria with one membrane (monoderms), an important mechanism of horizontal gene transfer. Here, we report the results of genomic, phylogenetic, and structural analyses of ComGC, the major pilin subunit of Com pili. By performing a global comparative analysis, we show that Com pili genes are virtually ubiquitous in Bacilli, a major monoderm class of Firmicutes. This also revealed that ComGC displays extensive sequence conservation, defining a monophyletic group among type IV pilins. We further report ComGC solution structures from two naturally competent human pathogens, Streptococcus sanguinis (ComGCSS) and Streptococcus pneumoniae (ComGCSP), revealing that this pilin displays extensive structural conservation. Strikingly, ComGCSS and ComGCSP exhibit a novel type IV pilin fold that is purely helical. Results from homology modeling analyses suggest that the unusual structure of ComGC is compatible with helical filament assembly. Because ComGC displays such a widespread distribution, these results have implications for hundreds of monoderm species.

Much of our current knowledge of biological chemistry is founded in the structure-function relationship, whereby sequence determines structure that determines function. Thus, the discovery that a large fraction of the proteome is intrinsically disordered, while being functional, has revolutionized our understanding of proteins and raised new and interesting questions. Many intrinsically disordered proteins (IDPs) have been determined to undergo a disorder-to-order transition when recognizing their physiological partners, suggesting that their mechanisms of folding are intrinsically different from those observed in globular proteins. However, IDPs also follow some of the classic paradigms established for globular proteins, pointing to important similarities in their behavior. In this review, we compare and contrast the folding mechanisms of globular proteins with the emerging features of binding-induced folding of intrinsically disordered proteins. Specifically, whereas disorder-to-order transitions of intrinsically disordered proteins appear to follow rules of globular protein folding, such as the cooperative nature of the reaction, their folding pathways are remarkably more malleable, due to the heterogeneous nature of their folding nuclei, as probed by analysis of linear free-energy relationship plots. These insights have led to a new model for the disorder-to-order transition in IDPs termed “templated folding,” whereby the binding partner dictates distinct structural transitions en route to product, while ensuring a cooperative folding.

Arrestin-1 is the arrestin family member responsible for inactivation of the G protein–coupled receptor rhodopsin in photoreceptors. Arrestin-1 is also well-known to interact with additional protein partners and to affect other signaling cascades beyond phototransduction. In this study, we investigated one of these alternative arrestin-1 binding partners, the glycolysis enzyme enolase-1, to map the molecular contact sites between these two proteins and investigate how the binding of arrestin-1 affects the catalytic activity of enolase-1. Using fluorescence quench protection of strategically placed fluorophores on the arrestin-1 surface, we observed that arrestin-1 primarily engages enolase-1 along a surface that is opposite of the side of arrestin-1 that binds photoactivated rhodopsin. Using this information, we developed a molecular model of the arrestin-1–enolase-1 complex, which was validated by targeted substitutions of charge-pair interactions. Finally, we identified the likely source of arrestin's modulation of enolase-1 catalysis, showing that selective substitution of two amino acids in arrestin-1 can completely remove its effect on enolase-1 activity while still remaining bound to enolase-1. These findings open up opportunities for examining the functional effects of arrestin-1 on enolase-1 activity in photoreceptors and their surrounding cells.

Ole Schmitz
Dec 1, 2004; 53:S233-S238
Section V: The Incretin Pathway

Andrew S. Kimball
Sep 1, 2017; 66:2459-2471
Immunology and Transplantation

David J. Hodson
May 1, 2020; 69:864-866
Commentaries

Mandeep Bajaj
Nov 1, 2005; 54:3148-3153
Metabolism

Maria Sörhede Winzell
Dec 1, 2004; 53:S215-S219
Section V: The Incretin Pathway

Christer S. Andreassen
Mar 1, 2006; 55:806-812
Complications

Lena Eliasson
May 1, 2020; 69:804-812
Small Noncoding RNAs in Diabetes

Mandeep Bajaj
Dec 1, 2012; 61:3078-3080
Commentary

Anne Jörns
Apr 1, 2020; 69:624-633
Islet Studies

Luigi Fontana
Apr 1, 2007; 56:1010-1013
Metabolism

Jens Juul Holst
Dec 1, 2004; 53:S197-S204
Section V: The Incretin Pathway

Sarah M. Gray
Dec 1, 2014; 63:3992-3997
Perspectives in Diabetes

Mariam Alatrach
Apr 1, 2020; 69:681-688
Pathophysiology

Jennifer Vogel
May 1, 2020; 69:1032-1041
Pharmacology and Therapeutics

Roy Taylor
Apr 1, 2012; 61:778-779
Commentary

Kristian Löbner
Mar 1, 2006; 55:792-797
Pathophysiology

Errol B. Marliss
Feb 1, 2002; 51:S271-S283
Section 6: Pusatile and Phasic Insulin Release in Normal and Diabetic Men

Meritxell Morró
May 1, 2020; 69:927-939
Islet Studies

Miriam Cnop
Dec 1, 2005; 54:S97-S107
Section III: Inflammation and beta-Cell Death

Patrice D. Cani
Jul 1, 2007; 56:1761-1772
Obesity Studies

Marlou L. Dirks
Oct 1, 2016; 65:2862-2875
Metabolism

Gordon C. Weir
Dec 1, 2004; 53:S16-S21
Section I: Insulin Resistance-Beta-Cell Connection in Type 2 Diabetes

Ralph A. DeFronzo
Apr 1, 2009; 58:773-795
Banting Lecture

Patrick E. MacDonald
Dec 1, 2002; 51:S434-S442
Section 5: Beta-Cell Stimulus-Secretion Coupling: Hormonal and Pharmacological Modulators

Gunnar Stenström
Dec 1, 2005; 54:S68-S72
Section II: Type 1-Related Forms of Diabetes

Elisabeth F.C. van Rossum
Oct 1, 2002; 51:3128-3134
Genetics

Jay S. Skyler
Feb 1, 2017; 66:241-255
Perspectives in Diabetes

VOLUME 285 (2010) PAGES 13742–13747In Fig. 1E, passage 10, the splicing of a non-adjacent lane from the same immunoblot was not marked. This error has now been corrected and does not affect the results or conclusions of this work.jbc;295/16/5533/F1F1F1Figure 1E.

VOLUME 295 (2020) PAGES 3285–3300An incorrect graph was used in Fig. 5C. This error has now been corrected. Additionally, some of the statistics reported in the legend and text referring to Fig. 5C were incorrect. The F statistics for Fig. 5C should state Fken(3,16) = 7.454, p < 0.01; FCCCP(1,16) = 102.9, p < 0.0001; Finteraction(3,16) = 7.480, p < 0.01. This correction does not affect the results or conclusions of this work.jbc;295/17/5835/F5F1F5Figure 5C.

VOLUME 294 (2019) PAGES 2555–2568Due to publisher error, “150 l/mm” was changed to “150 liters/mm” in the second paragraph of the “Vibrational spectroscopy of samples” section under “Experimental Procedures.” The correct phrase should be “150 l/mm.”

VOLUME 295 (2020) PAGES 1898–1914Yichen Zhong's name was misspelled. The correct spelling is shown above.

VOLUME 295 (2020) PAGES 4079–4092There was an error in the abstract. “The pyridinium cation hampers uptake of OPs into the central nervous system (CNS)” should read as “The pyridinium cation hampers uptake into the central nervous system (CNS).”

VOLUME 287 (2012) PAGES 44508–44517In Fig. 1A, the wrong image for the control group was presented. The authors inadvertently cropped the control images in Fig. 1, A and E, from the same raw image. Fig. 1A has now been corrected and does not affect the results or conclusions of the work. The authors sincerely apologize for their mistake during figure preparation and for any inconvenience this may have caused readers.jbc;295/19/6781/F1F1F1Figure 1A.

Frank Robinson's tenure as Giants manager was short but significant. He and his teams provided hope and promise when both were in short supply around Candlestick Park.

Do you think the Giants are just waiting around and could go after Bryce Harper for a big splash? Beat reporter Maria Guardado answers this question and more from fans.

Buster Posey plans to be on the field when Giants pitchers and catchers begin their first workout at Scottsdale Stadium on Wednesday, and if his rehab from right hip surgery continues to go well, he expects the same for Opening Day.

Giants president of baseball operations Farhan Zaidi would prefer to stay mum when it comes to his forays into the free-agent market, but he realized there was no use in attempting to obscure the club's meeting with superstar Bryce Harper in Las Vegas earlier this week.

Twenty-seven years after signing Barry Bonds to a then-record free-agent contract, the Giants are in the market for yet another superstar outfielder. San Francisco's interest in Bryce Harper remained a prominent topic of conversation during Saturday's FanFest at Oracle Park, with CEO Larry Baer weighing in on the potential franchise-altering benefits of landing a marquee player.

With Spring Training set to kick off Tuesday, it feels like an opportune time to put together a way-too-early look at who might be with the Giants when they begin their regular season against the Padres on March 28.

One year after making a pair of high-profile acquisitions in Andrew McCutchen and Evan Longoria, the Giants have experienced a far slower and quieter winter, leaving the club with quite a few question marks as pitchers and catchers reported to Scottsdale, Ariz., for the start of Spring Training on Tuesday.

The Giants added another arm into their bullpen mix Wednesday, acquiring right-hander Trevor Gott from the Nationals for cash considerations.

The Giants have expressed a desire to add multiple veteran outfielders throughout the offseason, and they made their first notable acquisition earlier this week after signing Gerardo Parra to a Minor League contract.

The road back from Tommy John surgery is often long and tedious, but Giants right-hander Johnny Cueto has a notable milestone approaching.

Steven Duggar and Ryder Jones continue to take steps forward in their rehab, as they were both cleared to take batting practice on the field Friday for the first time since their September surgeries.

Seeking to bring another versatile infielder into the fold, the Giants on Friday agreed to terms with Yangervis Solarte on a Minor League contract with an invitation to Major League Spring Training.