+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Dynamic motions of CD39 transmembrane domains regulate and are regulated by the enzymatic active site

, : Dynamic motions of CD39 transmembrane domains regulate and are regulated by the enzymatic active site. Biochemistry 43(43): 13849-13858

The two transmembrane domains flanking the active site of CD39 regulate its activity, but little is known about the structural and dynamic features underlying their importance. Here we use a disulfide crosslinking strategy to examine transmembrane helix interactions and dynamics and to correlate these features with activity and substrate binding. We find strong intrasubunit TM1-TM2 interactions, as well as TM1-TM1' and TM2-TM2' interactions between dimer subunits, near the extracellular side of the membrane but only weak interactions near the cytoplasmic end. The specific helix faces that constitute each interface are highly flexible, indicating a significant degree of rotational mobility within the packed structure. Analysis of activity after locking the helices in various orientations via disulfide bonds suggests that not only the arrangement but also the ability of the helices to move relative to each other is crucial for enzyme function. Helix mobility is in turn modulated by substrate binding. These results suggest that rather than playing a static structural role to support an optimal active site conformation, the transmembrane domains undergo dynamic motions that underlie their functional relationship with the active site.


PMID: 15504047

DOI: 10.1021/bi048644x

Other references

Ogura H.; Kubota M., 1985: Experimental studies on the transport mechanism of iron in rat incisor an autoradiographic study using iron 55 ferric chloride and colchicine. Japanese Journal of Pharmacology 39(SUPPL): 333P

Yang, C.; Shih, J.; Chao, T.; Tsai, C.; Yu, C.; Yang, P.; Streit, M.; Shahidi, M.; Miller, V.A., 2016: Use of BIBW 2992, a novel irreversible EGFR/HER2 TKI, to induce regression in patients with adenocarcinoma of the lung and activating EGFR mutations: Preliminary results of a single-arm phase II clinical trial. NlmCategory="UNASSIGNED">8026 Background: BIBW 2992 is a highly potent dual EGFR and HER2 inhibitor with preclinical activity in cell lines harboring EGFR activating mutations (H1650, IC<sub>50</sub>=0.7 nM) as well as tho...

Johnson, C.M.; Anderson, J.R., 1977: When the patient wants facial cosmetic surgery. Cosmetic facial surgery can improve appearance but it cannot make everyone beautiful (or handsome) or solve all problems. The patient must be well motivated and must comprehend the limitations of the procedures. Procedures useful in providing a mo...

Mike,L.; Baciu,A.; Popa,D.; Bozesan,I.; Bodea,D., 2008: Selection of maintaining, method for keeping of biological purity, patternship and health, regarding viruses infection of distinguished potato breeding lines. A large number of potato varieties and distinguished breeding lines disappeared as an effect of nonfavourable climatically conditions and especially by viruses diseases, as well as other biological and viruses degeneration. To avoid the negative e...

Tanaka, S.; Okada, M.; Murakami, M.; Hirakawa, M.; Manaka, S.; Nagashima, T., 1995: Human interferon-beta therapy for cerebral primitive neuroectodermal tumors: Two cases reports. A 5-year-old girl and a 2-year-old boy presented with recurrent cerebral primitive neuroectodermal tumor (PNET) and were treated with intravenous administration of human fibroblast interferon (HuIFN-beta) which was continued as outpatient maintena...

Just, O., 1952: Appreciation of degree of anesthesia by psychogalvanic reflex. Anesthesie et Analgesie 9(1): 17-19

Bishwajit, G.; Tang, S.; Yaya, S.; He, Z.; Feng, Z., 2016: Lifestyle Behaviors, Subjective Health, and Quality of Life Among Chinese Men Living With Type 2 Diabetes. NlmCategory="UNASSIGNED">The aim of the present study was to investigate the association between self-reported health (SRH) and quality of life (QoL) with five lifestyle-related behaviors including tobacco smoking, drinking alcohol, p...

Ganelina, I.E.; Churin, V.D., 1970: Once more on evaluating the effectiveness of various methods of treatment, in particular with anticoagulants, of acute myocardial infarct. Kardiologiia 10(8): 149-152

SoRelle, R., 2004: Breast-feeding may reduce later blood pressure. Circulation 109(10): E9017-E9027

Thormodsson, F.R.; Olafsson, I.H., 2005: Isolation and culturing of human vascular smooth muscle cells. Cerebral amyloid angiopathy (CAA) results from amyloid accumulation within arteries of the cerebral cortex and leptomeninges. This condition is age-related, especially prevalent in Alz-heimer's disease (AD), and the main feature of certain he...