scholarly journals Structural basis of transmembrane domain interactions in integrin signaling

2010 ◽  
Vol 4 (2) ◽  
pp. 243-248 ◽  
Author(s):  
Tobias S. Ulmer
Keyword(s):  
Transmembrane Domain ◽  
Structural Basis ◽  
Integrin Signaling ◽  
Domain Interactions

scholarly journals Prefusion structure of human cytomegalovirus glycoprotein B and structural basis for membrane fusion

2021 ◽  
Vol 7 (10) ◽  
pp. eabf3178
Author(s):  
Yuhang Liu ◽  
Kyle P. Heim ◽  
Ye Che ◽  
Xiaoyuan Chi ◽  
Xiayang Qiu ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Human Cytomegalovirus ◽  
Transmembrane Domain ◽  
Proximal Region ◽  
Viral Envelope ◽  
Vaccine Antigen ◽  
Glycoprotein B ◽  
Structural Basis ◽  
Fusion Inhibitor ◽  
Host Cell Membrane

Human cytomegalovirus (HCMV) causes congenital disease with long-term morbidity. HCMV glycoprotein B (gB) transitions irreversibly from a metastable prefusion to a stable postfusion conformation to fuse the viral envelope with a host cell membrane during entry. We stabilized prefusion gB on the virion with a fusion inhibitor and a chemical cross-linker, extracted and purified it, and then determined its structure to 3.6-Å resolution by electron cryomicroscopy. Our results revealed the structural rearrangements that mediate membrane fusion and details of the interactions among the fusion loops, the membrane-proximal region, transmembrane domain, and bound fusion inhibitor that stabilized gB in the prefusion state. The structure rationalizes known gB antigenic sites. By analogy to successful vaccine antigen engineering approaches for other viral pathogens, the high-resolution prefusion gB structure provides a basis to develop stabilized prefusion gB HCMV vaccine antigens.

Structural Basis for Dimerization of the BNIP3 Transmembrane Domain,

Biochemistry ◽  
2009 ◽  
Vol 48 (23) ◽  
pp. 5106-5120 ◽  
Author(s):  
Endah S. Sulistijo ◽  
Kevin R. MacKenzie
Keyword(s):  
Transmembrane Domain ◽  
Structural Basis

scholarly journals Structural Basis of SNT PTB Domain Interactions with Distinct Neurotrophic Receptors

2000 ◽  
Vol 6 (4) ◽  
pp. 921-929 ◽  
Author(s):  
Christophe Dhalluin ◽  
Kelley S Yan ◽  
Olga Plotnikova ◽  
Kyung W Lee ◽  
Lei Zeng ◽  
...  
Keyword(s):  
Structural Basis ◽  
Domain Interactions ◽  
Neurotrophic Receptors ◽  
Ptb Domain

scholarly journals Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids

2016 ◽  
Vol 148 (3) ◽  
pp. 227-237 ◽  
Author(s):  
Sun-Joo Lee ◽  
Feifei Ren ◽  
Eva-Maria Zangerl-Plessl ◽  
Sarah Heyman ◽  
Anna Stary-Weinzinger ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Membrane Lipids ◽  
Inward Rectifier ◽  
Primary Site ◽  
Structural Basis ◽  
Channel Activity ◽  
Anionic Phospholipid ◽  
X Ray ◽  
Anionic Phospholipids ◽  
Kir Channel

Inward rectifier potassium (Kir) channel activity is controlled by plasma membrane lipids. Phosphatidylinositol-4,5-bisphosphate (PIP2) binding to a primary site is required for opening of classic inward rectifier Kir2.1 and Kir2.2 channels, but interaction of bulk anionic phospholipid (PL−) with a distinct second site is required for high PIP2 sensitivity. Here we show that introduction of a lipid-partitioning tryptophan at the second site (K62W) generates high PIP2 sensitivity, even in the absence of PL−. Furthermore, high-resolution x-ray crystal structures of Kir2.2[K62W], with or without added PIP2 (2.8- and 2.0-Å resolution, respectively), reveal tight tethering of the C-terminal domain (CTD) to the transmembrane domain (TMD) in each condition. Our results suggest a refined model for phospholipid gating in which PL− binding at the second site pulls the CTD toward the membrane, inducing the formation of the high-affinity primary PIP2 site and explaining the positive allostery between PL− binding and PIP2 sensitivity.

scholarly journals Structural basis for cholesterol transport-like activity of the Hedgehog receptor Patched

2018 ◽  
Author(s):  
Yunxiao Zhang ◽  
David P. Bulkley ◽  
Kelsey J. Roberts ◽  
Yao Xin ◽  
Daniel E. Asarnow ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Extracellular Domain ◽  
Structural Basis ◽  
Cholesterol Transport ◽  
Common Cause ◽  
Common Receptor

AbstractHedgehog protein signals mediate tissue patterning and maintenance via binding to and inactivation of their common receptor Patched, a twelve-transmembrane protein that otherwise would suppress activity of the seven-transmembrane protein, Smoothened. Loss of Patched function, the most common cause of basal cell carcinoma, permits unregulated activation of Smoothened and of the Hedgehog pathway. A cryo-EM structure of the Patched protein reveals striking transmembrane domain similarities to prokaryotic RND transporters. The extracellular domain mediates association of Patched monomers in an unusual dimeric architecture that implies curvature in the associated membrane. A central conduit with cholesterol-like contents courses through the extracellular domain and resembles that used by other RND proteins to transport substrates, suggesting Patched activity in cholesterol transport. Patched expression indeed reduces cholesterol activity in the inner leaflet of the plasma membrane, in a manner antagonized by Hedgehog stimulation and with implications for regulation of Smoothened.

scholarly journals Structural Basis for Effector Transmembrane Domain Recognition by Type VI Secretion System Chaperones

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
John Whitney ◽  
Shehryar Ahmad ◽  
Kara Tsang ◽  
Kartik Sachar ◽  
Andrew McArthur ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Secretion System ◽  
Structural Basis ◽  
Type Vi Secretion System ◽  
Type Vi Secretion

scholarly journals The structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by TRC35

2017 ◽  
Author(s):  
Jee-Young Mock ◽  
Yue Xu ◽  
Yihong Ye ◽  
William M. Clemons
Keyword(s):  
Nuclear Localization ◽  
Protein Targeting ◽  
Protein Quality ◽  
Transmembrane Domain ◽  
Retention Factor ◽  
Structural Basis ◽  
Nuclear Localization Sequence ◽  
Trimeric Complex ◽  
Localization Sequence ◽  
Binding Groove

AbstractThe metazoan protein BCL2-associated athanogene cochaperone 6 (Bag6) forms a hetero-trimeric complex with ubiquitin-like 4A (Ubl4A) and transmembrane domain recognition complex 35 (TRC35). This Bag6 complex is involved in tail-anchored protein targeting and various protein quality control pathways in the cytosol as well as regulating transcription and histone methylation in the nucleus. Here we present a crystal structure of Bag6 and its cytoplasmic retention factor TRC35, revealing that TRC35 is remarkably conserved throughout opisthokont lineage except at the C-terminal Bag6-binding groove, which evolved to accommodate a novel metazoan factor Bag6. Remarkably, while TRC35 and its fungal homolog guided entry of tail-anchored protein 4 (Get4) utilize a conserved hydrophobic patch to bind their respective C-terminal binding partners Bag6 and Get5, Bag6 wraps around TRC35 on the opposite face relative to the Get4-5 interface. We further demonstrate that the residues involved in TRC35 binding are not only critical for occluding the Bag6 nuclear localization sequence from karyopherin α binding to retain Bag6 in the cytosol, but also for preventing TRC35 from succumbing to RNF126-mediated ubiquitylation and degradation. The results provide a mechanism for regulation of Bag6 nuclear localization and the functional integrity of the Bag6 complex in the cytosol.

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