WARWICKER Jim

Charged residues next to transmembrane regions revisited: "Positive-inside rule" is complemented by the "negative inside depletion/outside enrichment rule"

BACKGROUND:
Transmembrane helices (TMHs) frequently occur amongst protein architectures as means for proteins to attach to or embed into biological membranes. Physical constraints such as the membrane's hydrophobicity and electrostatic potential apply uniform requirements to TMHs and their flanking regions; consequently, they are mirrored in their sequence patterns (in addition to TMHs being a span of generally hydrophobic residues) on top of variations enforced by the specific protein's biological functions.

RESULTS:

type: 
Journal Paper
journal: 
BMC Biology 2017 Jul 24;15(1):66. doi: 10.1186/s12915-017-0404-4
pubmed: 
28738801
Url: 
https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0404-4
Impact Factor: 
6.779
Date of acceptance: 
2017-08-07

Energetics and Dynamics Across the Bcl-2-Regulated Apoptotic Pathway Reveal Distinct Evolutionary Determinants of Specificity and Affinity

Critical regulatory pathways are replete with instances of intra- and interfamily protein-protein interactions due to the pervasiveness of gene duplication throughout evolution. Discerning the specificity determinants within these systems has proven a challenging task. Here, we present an energetic analysis of the specificity determinants within the Bcl-2 family of proteins (key regulators of the intrinsic apoptotic pathway) via a total of ∼20 μs of simulation of 60 distinct protein-protein complexes.

type: 
Journal Paper
journal: 
Structure, Vol 24, Issue 11, pg 2024-2033, 1 Nov 2016, doi: 10.1016/j.str.2016.09.006
pubmed: 
27773689
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/27773689
Impact Factor: 
5.237
Date of acceptance: 
2016-09-28
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